Aluminium lithium hydride → 3-cyclopentyl-N-(4-hydroxymethyl-thiazol-2-yl)-2-(4-phenoxy-phenyl)-propionamide

HRID 1935225Notes

Reaction equation

C([O:3][C:4]([C:6]1[N:7]=[C:8]([NH:11][C:12](=[O:33])[CH:13]([C:20]2[CH:25]=[CH:24][C:23]([O:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:22][CH:21]=2)[CH2:14][CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[S:9][CH:10]=1)=O)C.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C(OCC)C.O>[CH:15]1([CH2:14][CH:13]([C:20]2[CH:21]=[CH:22][C:23]([O:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:24][CH:25]=2)[C:12]([NH:11][C:8]2[S:9][CH:10]=[C:6]([CH2:4][OH:3])[N:7]=2)=[O:33])[CH2:16][CH2:17][CH2:18][CH2:19]1

Participants

Conditions

Temperature: 25 °C

Procedure

A solution of 2-[3-cyclopentyl-2-(4-phenoxy-phenyl)-propionylamino]-thiazole-4-carboxylic acid ethyl ester (100 mg, 0.22 mmol) in diethyl ether (10 mL) was cooled to 0° C. and then treated with lithium aluminum hydride (13 mg, 0.32 mmol). The reaction mixture was slowly warmed to 25° C. where it was stirred for 16 h. After this time, the reaction mixture was slowly diluted with water (5 mL) and then extracted with ethyl acetate (3×10 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 70/30 hexanes/ethyl acetate) afforded 3-cyclopentyl-N-(4-hydroxymethyl-thiazol-2-yl)-2-(4-phenoxy-phenyl)-propionamide (50 mg, 55%) as a white solid: mp 83.7-87° C.; EI-HRMS m/e calcd for C24H26N2O3S (M+) 422.1664, found 422.1674.

Workup

extractionextracted with ethyl acetate (3×10 mL)
dry with materialThe combined organic extracts were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-c5c430e3bf234b98a75f06c05fbcb91d
Source dataset: uspto-grants-2002_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06384220B2

Reaction notes

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