Cesium carbonate → 4-[3-{6-[5-(3,3-Difluoro-pyrrolidine-1-carbonyl)-3'-fluoro-biphenyl-3-yloxy]-hexyl}-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester

HRID 1670126Notes

Reaction equation

HRID 1670126 reaction equation
[CH2:1]([O:3][C:4](=[O:48])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:23]=[C:24]([C:33]3[CH:38]=[CH:37][C:36](F)=[C:35]([F:40])[CH:34]=3)[CH:25]=[C:26]([C:28](=[O:32])[N:29]([CH3:31])[CH3:30])[CH:27]=2)[C:10]=1[CH2:41][CH2:42][C:43]([O:45][CH2:46][CH3:47])=[O:44])[CH3:2].C(OC(=O)CCCOC1C=CC=C(CCCCCCOC2C=C(C(N3CC[C:80]([F:84])([F:83])[CH2:79]3)=O)C=C(Br)C=2)C=1CCC(OCC)=O)C.FC1C=C(B(O)O)C=CC=1.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]>[CH2:1]([O:3][C:4](=[O:48])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:23]=[C:24]([C:33]3[CH:38]=[CH:37][CH:36]=[C:35]([F:40])[CH:34]=3)[CH:25]=[C:26]([C:28]([N:29]3[CH2:31][CH2:79][C:80]([F:84])([F:83])[CH2:30]3)=[O:32])[CH:27]=2)[C:10]=1[CH2:41][CH2:42][C:43]([O:45][CH2:46][CH3:47])=[O:44])[CH3:2]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 27339863-Fluorophenylboronic acidHCID 67337985HCID 67337985, compoundHCID 67339165HCID 67339165, compound

Product 1

HCID 673382034-[3-{6-[5-(3,3-Difluoro-pyrrolidine-1-carbonyl)-3'-fluoro-biphenyl-3-yloxy]-hexyl}-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl esterYield 97%

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-(3,3-difluoro-pyrrolidine-1-carbonyl)-phenoxy]-hexyl}-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester (112 mg, 0.16 mmol), 3-fluorophenylboronic acid (45.23 mg, 0.32 mmol), PdCl2(dppf) (17.63 mg, 0.024 mmol) and cesium carbonate (105.6 mg, 0.32 mmol) in 1,2-dimethoxyethane (5.0 mL) to obtain 4-[3-{6-[5-(3,3-difluoro-pyrrolidine-1-carbonyl)-3′-fluoro-biphenyl-3-yloxy]-hexyl}-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester (111 mg, 97%) as a colorless oil.

Sources & evidence

ORD record
ord-00ed97b79d2543eebb8e340580266e45
Source dataset
uspto-grants-2011_08
Patent number
US07989454B2

Reaction notes

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