Cesium carbonate → 4-[3-{6-[5-(2-Difluoromethoxy-benzylcarbamoyl)-2'-fluoro-biphenyl-3-yloxy]-hexyl}-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester

HRID 1670128Notes

Reaction equation

HRID 1670128 reaction equation
C(OC(=O)CCCOC1C=CC=C(CCCCCCOC2C=C([C:33]3[CH:38]=[CH:37][C:36](F)=[C:35]([F:40])[CH:34]=3)C=C(C(=O)N(C)C)C=2)C=1CCC(OCC)=O)C.[CH2:49]([O:51][C:52](=[O:98])[CH2:53][CH2:54][CH2:55][O:56][C:57]1[CH:62]=[CH:61][CH:60]=[C:59]([CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][O:69][C:70]2[CH:75]=[C:74]([C:76](=[O:89])[NH:77][CH2:78][C:79]3[CH:84]=[CH:83][CH:82]=[CH:81][C:80]=3[O:85][CH:86]([F:88])[F:87])[CH:73]=[C:72](Br)[CH:71]=2)[C:58]=1[CH2:91][CH2:92][C:93]([O:95][CH2:96][CH3:97])=[O:94])[CH3:50].FC1C=CC=CC=1B(O)O.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:49]([O:51][C:52](=[O:98])[CH2:53][CH2:54][CH2:55][O:56][C:57]1[CH:62]=[CH:61][CH:60]=[C:59]([CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][O:69][C:70]2[CH:71]=[C:72]([C:36]3[CH:37]=[CH:38][CH:33]=[CH:34][C:35]=3[F:40])[CH:73]=[C:74]([C:76](=[O:89])[NH:77][CH2:78][C:79]3[CH:84]=[CH:83][CH:82]=[CH:81][C:80]=3[O:85][CH:86]([F:88])[F:87])[CH:75]=2)[C:58]=1[CH2:91][CH2:92][C:93]([O:95][CH2:96][CH3:97])=[O:94])[CH3:50]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 27343542-Fluorophenylboronic acidHCID 67338951HCID 67338951, compoundHCID 67339165HCID 67339165, compound

Product 1

HCID 673379514-[3-{6-[5-(2-Difluoromethoxy-benzylcarbamoyl)-2'-fluoro-biphenyl-3-yloxy]-hexyl}-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl esterYield 84%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

The title compound was prepared by the same method as 4-{3-[6-(5-dimethylcarbamoyl-3′,4′-difluoro-biphenyl-3-yloxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy}-butyric acid ethyl ester starting from 4-[3-{6-[3-bromo-5-(2-difluoromethoxy-benzylcarbamoyl)-phenoxy]-hexyl}-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester (150 mg, 0.196 mmol), 2-fluoro-phenylboronic acid (55 mg, 0.392 mmol), PdCl2(dppf) (29 mg, 0.04 mmol) and cesium carbonate (128 mg, 0.392 mmol) in 1,2-dimethoxyethane (5.0 mL) to obtain 4-[3-{6-[5-(2-difluoromethoxy-benzylcarbamoyl)-2′-fluoro-biphenyl-3-yloxy]-hexyl}-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester (128 mg, 84%) as a colorless oil.

Sources & evidence

ORD record
ord-ca923257532342198a404fc52565dcf2
Source dataset
uspto-grants-2011_08
Patent number
US07989454B2

Reaction notes

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