Triphenylphosphine → [Rac]-3-(4-{2-[2-(3,5-dimethoxy-phenyl)-5-methyl-thiazol-4-yl]-ethoxy}-3,5-difluoro-phenyl)-2-ethoxy-propionic acid ethyl ester

HRID 394322Notes

Reaction equation

HRID 394322 reaction equation
[CH2:1]([O:3][C:4](=[O:19])[CH:5]([O:16][CH2:17][CH3:18])[CH2:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([OH:14])=[C:9]([F:15])[CH:8]=1)[CH3:2].[CH3:20][O:21][C:22]1[CH:23]=[C:24]([C:30]2[S:31][C:32]([CH3:38])=[C:33]([CH2:35][CH2:36]O)[N:34]=2)[CH:25]=[C:26]([O:28][CH3:29])[CH:27]=1.COC(=O)CC(=O)C(Br)C.COC1C=C(C=C(OC)C=1)C(N)=S.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[CH2:1]([O:3][C:4](=[O:19])[CH:5]([O:16][CH2:17][CH3:18])[CH2:6][C:7]1[CH:8]=[C:9]([F:15])[C:10]([O:14][CH2:36][CH2:35][C:33]2[N:34]=[C:30]([C:24]3[CH:25]=[C:26]([O:28][CH3:29])[CH:27]=[C:22]([O:21][CH3:20])[CH:23]=3)[S:31][C:32]=2[CH3:38])=[C:11]([F:13])[CH:12]=1)[CH3:2]

Participants

8

Reactant 6

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 27584913,5-DimethoxythiobenzamideHCID 9815681Methyl 4-bromo-3-oxopentanoateHCID 226474532-[2-(3,5-Dimethoxy-phenyl)-5-methyl-thiazol-4-yl)-ethanolHCID 59419836Ethyl 3-(3,5-difluoro-4-hydroxyphenyl)-2-ethoxypropanoate

Product 1

HCID 68617548[Rac]-3-(4-{2-[2-(3,5-dimethoxy-phenyl)-5-methyl-thiazol-4-yl]-ethoxy}-3,5-difluoro-phenyl)-2-ethoxy-propionic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In analogy to the procedure described in example 1 d], [rac]-3-(3,5-difluoro-4-hydroxy-phenyl)-2-ethoxy-propionic acid ethyl ester was reacted with 2-[2-(3,5-dimethoxy-phenyl)-5-methyl-thiazol-4-yl]-ethanol (prepared from [rac]-4-bromo-3-oxo-pentanoic acid methyl ester [PCT Int. Appl. (2001), WO 01/79202] and 3,5-dimethoxy-thiobenzamide [PCT Int. Appl. (1992), WO 92/09586 A1] in analogy to the procedures described in examples 12 a] and 12 b]) in tetrahydrofuran in the presence of triphenylphosphine and DEAD (diethyl azodicarboxylate) to yield [rac]-3-(4-{2-[2-(3,5-dimethoxy-phenyl)-5-methyl-thiazol-4-yl]-ethoxy}-3,5-difluoro-phenyl)-2-ethoxy-propionic acid ethyl ester, which was further saponified in analogy to the procedure described in example 4 e], to yield [rac]-3-(4-{2-[2-(3,5-dimethoxy-phenyl)-5-methyl-thiazol-4-yl]-ethoxy}-3,5-difluoro-phenyl)-2-ethoxy-propionic acid as colorless solid.

Workup

  1. customdescribed in example 1 d

Sources & evidence

ORD record
ord-6410be7c01d54dc7b8d203013ac56195
Source dataset
uspto-grants-2004_10
Patent number
US06809110B2

Reaction notes

Loading…