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

HRID 394321Notes

Reaction equation

HRID 394321 reaction equation
[CH2:1]([O:3][C:4](=[O:21])[CH:5]([O:18][CH2:19][CH3:20])[CH2:6][C:7]1[CH:12]=[C:11]([O:13][CH2:14][CH3:15])[C:10]([OH:16])=[CH:9][C:8]=1[F:17])[CH3:2].[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[S:30][C:31]([CH3:37])=[C:32]([CH2:34][CH2:35]O)[N:33]=2)=[CH:25][CH:24]=1.COC(=O)CC(=O)C(Br)C.ClC1C=CC(C(N)=S)=CC=1.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:21])[CH:5]([O:18][CH2:19][CH3:20])[CH2:6][C:7]1[CH:12]=[C:11]([O:13][CH2:14][CH3:15])[C:10]([O:16][CH2:35][CH2:34][C:32]2[N:33]=[C:29]([C:26]3[CH:27]=[CH:28][C:23]([Cl:22])=[CH:24][CH:25]=3)[S:30][C:31]=2[CH3:37])=[CH:9][C:8]=1[F:17])[CH3:2]

Participants

8

Reactant 6

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 27348264-ChlorothiobenzamideHCID 9815681Methyl 4-bromo-3-oxopentanoateHCID 226476242-[2-(4-Chloro-phenyl)-5-methyl-thiazol-4-yl]-ethanolHCID 68617763[Rac]-2-ethoxy-3-(5-ethoxy-2-fluoro-4-hydroxy-phenyl)-propionic acid ethyl ester

Product 1

HCID 68617320[Rac]-3-(4-{2-[2-(4-chloro-phenyl)-5-methyl-thiazol-4-yl]-ethoxy}-5-ethoxy-2-fluoro-phenyl)-2-ethoxy-propionic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In analogy to the procedure described in example 4 d], [rac]-2-ethoxy-3-(5-ethoxy-2-fluoro-4-hydroxy-phenyl)-propionic acid ethyl ester [example 68 a]] was reacted with 2-[2-(4-chloro-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 4-chloro-thiobenzamide 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-(4-chloro-phenyl)-5-methyl-thiazol-4-yl]-ethoxy}-5-ethoxy-2-fluoro-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-(4-chloro-phenyl)-5-methyl-thiazol-4-yl]-ethoxy}-5-ethoxy-2-fluoro-phenyl)-2-ethoxy-propionic acid as light yellow solid.

Workup

  1. customdescribed in example 4 d

Sources & evidence

ORD record
ord-9df4425c3ba346fcbaf089373013790d
Source dataset
uspto-grants-2004_10
Patent number
US06809110B2

Reaction notes

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