Methanol → 2-(3,4-dichloro-phenyl)-3-(3-hydroxy-cyclopentyl)-N-thiazol-2-yl-propionamide

HRID 2214087Notes

Reaction equation

HRID 2214087 reaction equation
CO[C:3](=[O:20])[CH:4]([C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([Cl:19])[CH:13]=1)[CH2:5][CH:6]1[CH2:10][CH2:9][CH:8]([OH:11])[CH2:7]1.[NH2:21][C:22]1[S:23][CH:24]=[CH:25][N:26]=1.C[O-].[Mg+2].C[O-].CO>>[Cl:19][C:14]1[CH:13]=[C:12]([CH:4]([CH2:5][CH:6]2[CH2:10][CH2:9][CH:8]([OH:11])[CH2:7]2)[C:3]([NH:21][C:22]2[S:23][CH:24]=[CH:25][N:26]=2)=[O:20])[CH:17]=[CH:16][C:15]=1[Cl:18]

Participants

5

Reactant 4

HCID 887MethanolHCID 21552-AminothiazoleHCID 164537Methanol, magnesium salt (2:1)HCID 674821392-(3,4-Dichloro-phenyl)-3-(3-hydroxy-cyclopentyl)-propionic acid methyl ester

Product 1

HCID 100001392-(3,4-dichloro-phenyl)-3-(3-hydroxy-cyclopentyl)-N-thiazol-2-yl-propionamideYield 54%

Conditions

Temperature
110 °C

Procedure

A mixture of 2-(3,4-dichloro-phenyl)-3-(3-hydroxy-cyclopentyl)-propionic acid methyl ester (25 mg, 0.08 mmol) and 2-aminothiazole (9.4 mg, 0.09 mmol) in a solution of magnesium methoxide in methanol (7.4 wt. %, 0.22 mL, 0.15 mmol) was heated to 110° C. for 18 h. At this time, the reaction mixture was cooled to 25° C. and then filtered through a pad of celite (methylene chloride as eluent). The filtrate was washed with a 1N aqueous hydrochloric acid solution. The organics were dried over sodium sulfate, filtered and then concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 75/25 ethyl acetate/hexanes) afforded 2-(3,4-dichloro-phenyl)-3-(3-hydroxy-cyclopentyl)-N-thiazol-2-yl-propionamide (16.4 mg, 54%) as light tan oil: EI-HRMS m/e calcd for C17H18Cl2N2O2S (M+H)+ 385.0537, found 385.0542.

Workup

  1. temperatureAt this time, the reaction mixture was cooled to 25° C.
  2. filtrationfiltered through a pad of celite (methylene chloride as eluent)
  3. washThe filtrate was washed with a 1N aqueous hydrochloric acid solution
  4. dry with materialThe organics were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b3fa0af47904412ab5e7a8b75b86d58d
Source dataset
uspto-grants-2006_09
Patent number
US07105671B2

Reaction notes

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