Tetrahydrofuran → HCID 22315240, compound

HRID 398468Notes

Reaction equation

HRID 398468 reaction equation
COC([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:26])[CH:12]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)[CH2:13][CH:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)[S:8][CH:9]=1)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-].[O:33]1CCC[CH2:34]1>>[Cl:25][C:22]1[CH:21]=[CH:20][C:19]([CH:12]([CH2:13][CH:14]2[CH2:15][CH2:16][CH2:17][CH2:18]2)[C:11]([NH:10][C:7]2[S:8][C:9]([CH2:34][OH:33])=[CH:5][N:6]=2)=[O:26])=[CH:24][CH:23]=1

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 20707093HCID 20707093, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 22315240HCID 22315240, compoundYield 55.4%

Conditions

Temperature
0 °C

Procedure

A solution of 2-[2-(4-chloro-phenyl)-3-cyclopentyl-propionylamino]-thiazole-4-carboxylic acid methyl ester (prepared as in Example 32, 127.7 mg, 0.31 mmol) in tetrahydrofuran (0.4 mL) was added to a slurry of lithium aluminum hydride (15.0 mg, 0.39 mmol) in tetrahydrofuran (2.24 mL) at 0° C. The reaction mixture was stirred at 0° C. for 2 h. The reaction was then quenched by the dropwise addition of water. The reaction was then diluted with more water (25 mL) and extracted with ethyl acetate (3×25 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 75/25 hexanes/ethyl acetate) afforded 2-(4-chloro-phenyl)-3-cyclopentyl-N-(5-hydroxymethyl-thiazol-2-yl)-propionamide (63.4 mg, 55.4%) as a white solid: mp 115-117° C.; EI-HRMS m/e calcd for C18H21ClN2O2S (M+) 364.1012, found 364.1004.

Workup

  1. customThe reaction was then quenched by the dropwise addition of water
  2. additionThe reaction was then diluted with more water (25 mL)
  3. extractionextracted with ethyl acetate (3×25 mL)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e78e1452155a4b12a6dbd22cb1dd0f84
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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