Oxalyl chloride → {2-[3-Cyclopentyl-2-(4-fluoro-3-trifluoromethyl-phenyl)-propionylamino]-thiazol-4-yl}-acetic acid ethyl ester

HRID 398718Notes

Reaction equation

HRID 398718 reaction equation
[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[C:13]([C:18]([F:21])([F:20])[F:19])[CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[CH2:28]([O:30][C:31](=[O:39])[CH2:32][C:33]1[N:34]=[C:35]([NH2:38])[S:36][CH:37]=1)[CH3:29].C(N(CC)C(C)C)(C)C>C(Cl)Cl.CN(C)C=O.O1CCCC1>[CH2:28]([O:30][C:31](=[O:39])[CH2:32][C:33]1[N:34]=[C:35]([NH:38][C:8](=[O:10])[CH:7]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[C:13]([C:18]([F:21])([F:19])[F:20])[CH:12]=2)[CH2:6][CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)[S:36][CH:37]=1)[CH3:29]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 1044544-Thiazoleacetic acid, 2-amino-, ethyl esterHCID 120695003-Cyclopentyl-2-(4-fluoro-3-trifluoromethyl-phenyl)-propionic acid

Product 1

HCID 23394574{2-[3-Cyclopentyl-2-(4-fluoro-3-trifluoromethyl-phenyl)-propionylamino]-thiazol-4-yl}-acetic acid ethyl esterYield 53.9%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 3-cyclopentyl-2-(4-fluoro-3-trifluoromethyl-phenyl)-propionic acid (prepared as in Example 87, 250 mg, 0.82 mmol) in methylene chloride (8.22 mL) cooled to 0° C. was treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.45 mL, 0.90 mmol) and a few drops of N,N-dimethylformamide. The reaction mixture was stirred at 0° C. for 10 min and at 25° C. for 20 min. The reaction mixture was then treated with a solution of (2-amino-thiazol-4-yl)-acetic acid ethyl ester (337 mg, 1.81 mmol) in tetrahydrofuran (4.11 mL) and N,N-diisopropylethylamine (0.34 mL, 1.97 mmol). This solution was stirred at 25° C. for 18 h. At this time, the reaction was concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 75/25 hexanes/ethyl acetate) afforded {2-[3-cyclopentyl-2-(4-fluoro-3-trifluoromethyl-phenyl)-propionylamino]-thiazol-4-yl}-acetic acid ethyl ester (208.7 mg, 53.7%) as a pale-yellow gum: EI-HRMS m/e calcd for C21H22F4N2O3S (M+) 472.1444, found 472.1442.

Workup

  1. stirringThis solution was stirred at 25° C. for 18 h
  2. concentrationAt this time, the reaction was concentrated in vacuo

Sources & evidence

ORD record
ord-b8d6f371591443eab309c8b8c5be34e7
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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