Document gayQQyXL4LO2aYNr0e6XQ26Y3
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BESTCOPYAVALABLE 56
'
Synthesis and Guracterization of bo-us-lee |RECEIVED
December 28, 1978
||
|
LIoNtl ony
Conducted at:
CanodmmeRrickiearlLaCbhoeraaitcoarlisesD,iviIsnci.on 3St. Paul, Minnesota 55101
During:
April 1979 co July, 1979
Synthesis Conducted by:
FE. Behr
SFpuerciitfyicDetAcetrimviintaytioanndbyR:adiochemical
pasoct byt
3. D. Johnson and S. J. Gibson
Z=]AC TA' )
FReEse.arcDherS,pechioadl.ist Dace Comercial chemicals Division
HSCpheavcriafciitcersiAzcattiivointySeancdtioRnadiochemical
SeniD.orJopkfPdtenhemsicianl sPharmY acoTlaotO egist Riker Laboratories, Inc.
R~ ERa Jl.23]0c
MRaCnaEgerO,berD,ughoHbe.tabolisn ate Riker Laboratories, Inc.
CO2870
,
on
Summary
Tishelsaybneltehde)s.is Tohfeasp2e0c.i0figc laocttiofvitFyC-w1a4s3-1d4eCterimsindeedscrtiobebde 0(.c3a0r7bon+yl0.0c0a5rbon uatCi/lmega.st 9R8a%diopucrhee;mictahle FpuCr-i1t4y3-14gCtewramsinaftoiunodn sshuoiwteadbletheforFCm-e1t4a3-b1o4lcismtosebuedies. Introduction
wAFfaCrs-os1me4sr3yitnehsteahnedobsofidtyzeh.eexdpep"aroTnisodmseifncbathicsalirilatiictystaetborefeiizantefghdfeespecltaiennxngpeedrtihtmeoenritanstv,eescotfoigreabltoienm-it1nhaetlimaoebnetlaeobdfoliFFsCe-m-1lioi3fg-lic
Figure 1 is described.
. The synthetic pathway i1]ueteotod br
A. Synthesis of re-143-'c
I. Fractional Distillation of Cell Run, A-3265-8
cAcenolanlltyasidinrseadinbiyanbgogsuatswec1rh2er.o13dmraihteiodgghroavpbehoryiliasnnhghoywdemrdaotuetsrhieaKlFcse.lflo
dThreaineirnoggse remove NE.
TfFhoreractsdiiooslntisidlsl1 awteainroden.2rem(To3hv8re9e.de3 bygf)raf,citlwiteorrnaestiwocenormebtionceoyldileealcndtdedA.w3i4l(l0tabgbemisus1e)d.
for the preparation of Cf Low,.
11. HFyrdornolRy-s3i2s65-a8nd Stabilization of Distilled Cell brainings
eaIdqndutiiotpipaoend50w0fiutnmhlnelat,hmrececoehn-adnneeinccskaeelrd, sratoniudrnrde-trbh,eortmTtoormmuee-tdBeorrfelwaasskstwpilhraricecerhd.haastdhseenbgeieyn, macdiodxmeebddinestdoolucttehleilonfdlorafsakinNaitOnhRgrso,u(g6h8F.ra4a5c)ptiroenssasn|udrawenad-tee2qr,iuz3a(e86ld98..a34ddogif.tionwaAsfpunrnee-l ob9veethorwueres5n." m5i2An5futteeCrs. attheThae9rhmaoituxertusrurefefawicactsiioennhteattitemoed,keteotpherethpfeHl.uwxtaesm(8p5efroCan)tduroevro cb(oe2n5t7>e.n01t2s.m.l) TThahenedmi9fi6xn%taulrHeypSH0w,aswa(sc3o4o.<3le1dnl()tCoownag6so5Cardeddaenddpapaselrom)wi.lxytuTrtheoeotfhaecwiadFvilfeeirsekd m3tih5ex6t.ub7ro9ettwoams(f9hl1e.ua6o3treodcmahseasnticy8ai0lelCdp)hf:aosre 3w0asminsuetpeasr,atecdo.oledThetoyi6e5lCd. waned 11. T Fractional DistilrlaE etinonooffcG.hfibstoonM Tfflhaaeksek-a,opfpfaarahsetmaauldsl, cpaoancsckioesldtleedchteioaotfnedaasd5si0es0mtbimlllyl,atthi~ro7en8e-Cnceocclokulemdd, trprooauptn,d-tmbhaoegtrntmeoormmieseder, asrnatddiirorSaeucpretria-vsCeseelmfbllu(yo0,r.7ocah9n)edmiwacaasmleardc(du3er5dy6.7mtoang)ot,mheet9ed6r3i.scsiullTlfhaeutriibocansaecfcilsadtsak(n.1]2i.s0tehdenl),
02871
. BESTCO
bbwaoetileloriwng4a0smpCaitreaatrtioa2rl0s0vawmcemuruevnacwruaeusmmo,vaeddjt.uhestedAdsistttiholel2ah0te0iaodmnmtwaeanmsdperctaohtneutrilenouweddrooppned
aTnodwearnavlayczueudm b(y10g-a2s0 cmmh)r.omatForgarcatpihoyn.s werecol lected, weighed,
rfThoeerfraapcentraicloeynnstiasteCdw7aFs)1s3CdOog,nivHee b(9ySe5ea.r0eTaabClFp)eesrCc1Oe1T)nH.t
anFdractthieonass6aybhre0pogr.tedwoswas (see Table 111).
9F6r.a0c8ti%onCF3,|5C(O2,4H.)3 wge,re97c.o5%mbiC,fF1eL8d forHFu,seanidn pFrreapcatriaotnioAn o(f13F.4e-jg,is-lhc.
IV. ApFnHrhaywcdatsrioounrssecNh3eHcaknewddas4afa(td3ed0re.d02u5n)htoiuwlresr.ethedTihpseHsowlsavlseudrrgyrienwaatFseCr-8f0itlhta(en9r0e8d.m,l).aTnhde
sptorhleeipdaprreoadtduc6bt5yCpwauslfvoearriri1zihndogruire.tdhe iAanniartlhydesriihseodobdy.SoglaisdThceahnrdFoimndaartlyoignprgraopdhhuyeceshwoowsed
sofnoollialdossws,ianyg20o.fL0n5u58;m.b8e8Lr-sUCSFBw)6e,?.eCOfS,rs0ashciytginoendaT:theedyLTC-e;ulFsdydosl,v0asHFc,-3110iN1o3-T5gi2rc5,43T:ha8e-o30,
Fraction 4, 004 g.
8. Specific Activity Determination of Fe-143-''c
wTie0hnrrteeo1e0 tpmhrslretepaweanirdtea1hdr0dnmbleystohwclaelunaitosgilsohniaAsnngdvdopflt1hi,Femee-1tF01rl.4ia33cs6-k1snF%elc;wa2eskr1(se1L.,-mUi2sxTB5ehs.de,38vbsyoneglesuimSneayvsmneirtwtheie1rns1egi1"sauSsjeoscrstteieotns))
TaColailqitubhorrteasetedooffmetiahccehrvoispaolilsupteciootnnttoadwirienrsrietencgtluys1e0dIunlttooalasilcqiiuqnouttoistllaasntidixont1o0cotpiuhrnetaeinnggco5bny1stixaahiia8enn0sign.5g1
o5f0 Aulquaalsioqluotswefrreomadcdaecdh. Tphreimarreymaisnoilnugtiovni,als1 mwlereofpwraetpearredandwit1h5 m31.5 mi
ScotfoceuimnnmptteeeitrdhlaaltnautortwleioonatanniddnSepsea7cl.tal5rtoowmmle5edtmoeiftrno.uMteTeSqsSuTShi.eelaicbchroTauhtnweetiitshnaigmnapeltfePhfseaicckdwiaaeerrrdnkecyMbcoeodwfoeaolrsreedd33ett8tho5ee.ryrLme)iwfqnerueridegderfoartor
eraecdhucesdamptloedpbym atnhde are shown in Table
hti.hneteTurhCnaeil/mogvsetrwaaanlsdlarcdaavlemcreuatlghaeotde.dspefcToirhfeiecaacvhearcatvigiavelid.tydaTrbheaeseedderreoen
mtehaen 36uCir/enpglicfaotuensd the overall mean.
f(To1hr2eefamrceoahmnsoefacbhetthweweeeipngrhiiAmnaqgru)yaswowealisgha0in.nd5g0sN7TSw+Sas0w.ew0r1ie2thwiuinCtih/1in.ng8.%0o.f1T2h%e,
and the means between 10 ul and 50 ul aliquots were within 2.0%.
2 Riker Isotope Number 453.
bWaeliagnhciengwshiwcehrehaadccobmeepnlisrheecdentolnyaca5l-iplbarcaetedMetbytle3rh MHehtroelloegcyt.ronic
L/1 Hicropipettor, Lab Industries, Berkeley, CA.
2
New England Nuclear, Boston, Mass.
Modified T55:25.2 5 1.01 g Dimethyl
POPOP and
3.8
liters
toluene.
COR872
C. Radiochenical Purity Analysis of Fe-iz-'ic
+ Thin-Layer Chromatoaraphy Systems and Carbon-14 Analysis
TooaffaSktehcgniinay-lolyraeeyiesrrooufstyisrnteeedlmiysachdueesnviienclgaolpSeGdFpur2ini50ty1m0iwcasrxonc1a24rprrexiesdocroorutethdinUweintijhpasleaatevsar.iety
CTItuana2.sn%0tk5:o%5smmcwFaneidrtewetieddtaeelmlwpoislwteaghetmdeegnlttaoasns.dsdevleTihldeospascn1rd5apc|ininngaendwdawsiwetrahec.csoasctmruparrpaoetndieodnracopeairdsss!h.iVy
TgLoool)lSxheaeccttemldeytihn0a.n5soc,licnmt7wi.il5dltamhti.ioonfsThvhMaieIraSplsSescnrewcadaopsensdttaaisininillniegcsas2.gs5etlemeilseogsfmpeanmtteucslhsawmogerrsee.und
sbgcaorcuaknpoteredodunfadrnodnustbiheneglocwaountsthuseitoaprbeilrgeimnbilnoaunntketh((ecupsapmudl)adaletwldeye.rbetewTiochnoe0r.rs5eactcmenednsefoucrnoenmts
SSipcmh wesreeamennotl plate:
wcaosrreecxtperdessfeodr
aesffipceirecnecnyt. ofThteoctaalrbgcoaanrsbs1osany|ce-bodn)eteentcthreoe.f
TncopFm ocnp_soegnnenets x 100 = % carbon-14 content i; nsegnent.
sSThphegomweipnnetgrcentnuhntebercr.aadribooanThc-it1si4vipctroyonvtpieednaetkdsofacoterahrciehns-plsoaenygdenirenngt component
wraasdiopclhortetnesdtovpeernssus fo sepmcasey
s in the material applied to the plote.
!1- SoR slouluta tiioondUsUsei eddffooorr c Radih ocheemicaml PPui urrittyc yAnAa naallyysl sis
ph3jla9oac0oci,io72n1ng1u0t3.i00o.n39mlumsgecldaosftsoFACs-tv1ro4el3au-km1e4tthrei(ctRihkFielnra-slkaI,y3eoartdojppuelsattIiennsgv.ewnatsotrhyprNveupomarbreeesrd
by
459)
eOaFchthipslatsweoi.ltuhtimoenthawansol,appalnidedmixiinnag nbayrrhoanwdfobuyr ionnverrtoinngg.str`obnitreLoLoyo
111. RResueltssaanndudDiDlsisccutussssison
TYbShnyieanscSbreyeenlstteuhhdleetssiFcshCoe-fm1ai1nc3dtahlewgaassidcneohntrtoicmtoay-tcoohgfrroatmphahetyoFgC(r-sae1pe4h3es-de1c4wtCiitoihns
Aw.ellthiessrteasbglries)h,e the Feo1hg The)
gTpoppaeren3t aonnd orems did
nPiolntatFeirgeNsuourrlenavsbdeeir2o-tc6h2h.iesm(iFcAiaglusrmeaplul3r)i.taymoTuahnntealoyotsfhiesirmaprfueoruirtsytsoa(w+lv3ie5ns)
was
SbdhadyseoinmstaitofofygrgtaahpsehycI,hmrpotuhmr.aittoyrgardfaiopouchnhydemo(insicemaPcplltuiaroptinutery.iAu.tmybtNeohofrisart2e.tpemopbrtet)ewraasanldsaedteehintne-o.elayer
98%. The FC-143-c is suitable formetabol Ffoomtisso.udicUes.is me Teale
2
2
Analtech, 75
Supelco Inc.
Blue Hen Dri
Bellefonte,
ve, Newark,Delaware.
Fennsylvania.
02873
Acknowledgenent dTtohhneeeacuabtyrhbooMrrn.s-14TgordaldtaebMfealuteldhliysceealnclkonfdorwalCioenmdimgneegrscti,haelfrgCaashcetmiciohcnraaoltmseadtDoiagvcriiasdpi,hoinac.ndanTaFhlCey-s1ai4us3t-h1oo4frcs gHeraadtreifcukllyduraicnkgnowtlheedgeelectthreocahsesmiisctaalnceFlouforJionhantioCn. oHfansleanbeiaendd CLoar3ry00G..
COR874
-
List of sable and rigures
Table 1 Data from One Plate Distillation of Cell Fun R-3265-5.
NB 50942 p. 53 .
Sable 2: DB ata frome Fractional Distiliasion of Cytlog.
Taste 3: Date for Refractionasion of G6, 30.
NB 52343 p..8
Tig
Table 4: Seon Specific pan: Activity Determination of FC-143-1%c.
Table 5: Thin-layer Chromatography Systems for FC-143- %c. NB 51807 p. 35.
Figure 1: Pathway for Synthesis of rc-143-Yc. NB 52343 p.4, 5, 6, 8, 9.
Figuse 2: Thine-iearye.s fadiochromatogran, Plate i. Figure 3: TSoin7-tay5er Raadioc3h5:rosatosran, Plate 2. Figuce 4: TaaiSnieaayyes.taTdshoc:hzomatogran, Plate 3. Figuze 5: ThinE-ieaye.r Radiochzonatosran, Place 4. Figuce 6: Tphin-r iayesatadiochromacogran, Plate 5.
COR87S
--
Tate 1
Data trom One Plate Distillation of Cell Run, K-3265-3
Assay Gic (area Percent)
m--_--_o-- m we wers! 8 T oon.ece m? Tcoeme"r TmeTse
1 es ase ss mer ses 10.20 0
2 sos ama
a2 ees 25.50 0
soso oma
- nan 00.87 17.6
soteons
2a
Hostly High Boilers
----------------------------------------------
# 15's Hlonbotlers -- unidentified bue wich retention tines < GF,
Ci: Cg cylic other = various perfluorsbucyltecrahydrofuraus and isomers. a's inacerials boiling higher than CF, (COF.
C02876
"he
Table 2 Daca from Fractional Distillation of C,F, Co
Bx bpo2C
WI(g)
FE ETa
2 35-40
103.6
3 2647 om) 2.4
4 ss-101
2.1
5 101-103
1.2
6 06-109 (7mm) dio
Inerts
99.98 2.18 597 -- --
[3ZAFas1vs1aCey0o7n
CgF13C0pH
-9.41 13.19 15.85 5.19
F750150!
-87.9 79.8 78.8 90.3
GLC analysis of FR #6 showed about 3.9% high boiling materials .
CORE77?
E --_-- e) 1 en 0) 2 nas 3 ne "oe Ww
--
rable 3
Data for Refractionasion of CF,Lou
YiTeldT(8)F 1s 3.7 2%.3 13.4
"2.9 (1
Assay (Area 3) OC7sFy5o00,H3
89.03 97.26 97.5 96.08
Assay for input Co refractionation was 94.35% CF)CON analyzed as CF) sCO,CH | -_--
CO2878
_
BEST COPY AVA
Specific Activity betermination of FC-1643-19
Solution 1 10.5S6em3/10.0m1
G00.:i458s837 0G0.35i00s6%t1 ooi:iseiAa 0p0:5e:3i30]78 :35850.0124
Solution 11 25.2T808h/10.081
000:.:54239959 030..333005006687 H003:e53%3 o00::3331116600 3i65.0.0110
Sotucton 111 f20.0t6m5o/10.m081
oo0i.ii4d5ed6s6 0G6:r35i00e08s7 GP0:ie5s1t io03i0es% 3:3858:0.0056
Comparison of Scintillation Solvents
ar Aquaso1 0o0::.3440s808n7 00033:1133270s 0G0:r:5i3n93s eo0:ee35 O00irsiiose%ass ao0i.ii30i61
0.50740.0137
MwIiSrS a0oi.si5os0t6r1 0o0:3e:%0s53 000.3:3300600)6 00053:1330960 o:0.3e5o0r80e 005.e05s80t88
0.5068+0.0093
Goparisen of 1041 and 50u1 Aliquots
i 10ul o5G..4i3a08s%7 o0o.ls3is0st8y1 000.333239605s78 300:::33030868 O0Filiisenzas eoGiiiires
0.502120.0109
vm 50u1 oo0.i5s1s2 S00i3.d03e75s60 F00::e33 Fo0e:ee3s1 o0Gl:si3de0e 00G..4i5500s35
0.512120.0101
Overall average = 0.5071:0.01154Ci/mg
.
02879
To
Thin-Layer Chromatography Systems forre-143-Y4
nn
ee
TE
+
100 acetone
0.03
2 acetic acids
5 ammonium hydroxideS
- nn
2 Solvents were prepared volume:volume; a 100 ml aliquot of solvent mixture
t 1s of major (-:98%) pesk on the chin-layer chromatography place.
Acetic acid and ammonium hydroxide were concentrated.
COZ830
v
Figure 1
BESTTCCODPY Ava 4p.
Pathway for Synthesis of FC-143-Yc
ny to:ct
BErE.
PPraetphafriendderby Laboratories
rd
C7F15COF
one-rlate
Distillation
T+ Noon
BPulge;ss
1
FractLions al
IT + Ny
Fe e-80 ns
cp,so2 r 3256-3
2 C7F11 5COF
C7F115020,1
Refractionation
wm b+o,cor, Fo-143-14cd
>CyoFsyszto 1m Assay
#-Denotes position of Carbon-1 * re-143-Y, Amoniun perfluorooctancate
COR881
,.
90 os 0 7
0 es 6 Loss
EI
Eu
fw FEE ix
a 0 15 10 5 o
LE
i Figure 2 BESTCOPY AVA ABLE Te top mseerin of
SG Uniplaces 190 chlorarurn Total CP on Place = 99,892
EE
Distance from origin
(@
COR882
"
"
Zw iow Ew
0 .
-
Fe-143-14c, Plate No. 2
BEST COAVAPBYLE
see, scm ori (cM)
COR883
6
"
= 40
3 ow FEY
. .
Fe-143-14, Plate No. 3
BEST COPY Aishuii.
(a)
COR884
sigu5r BESTCOPY A4ii hate
Thinlayer adiochronatopean of
#C-143-14, plate No. 4
"
SOF Uniplate: 13300 cmehtlhoornootrars
5 Semonim bydronide
0
Total Ch on Place = 105,567
Fr
Zw
&
HE
0
o 1 * 3 {3 7353 TLE LTD biscance trom Origen
(an
CO2885
paus6e P[E restr -- ea-- ts w
so
SGF Uniplate: 10f0s mCoholmoersonftorhmparonia
i.
otal can on Pl=a10c7.1e20
iw
:
& 20
"
. C1: 3 4 567 53mm omen sistance@teem origin
COR886