Water → N-(4-{2-[3-fluoro-4-(hydroxymethyl)phenyl]ethyl}-1,3-thiazol-2-yl)acetamide

HRID 1892480Notes

Reaction equation

HRID 1892480 reaction equation
[C:1]([NH:4][C:5]1[S:6][CH:7]=[C:8]([CH2:10][CH2:11][C:12]2[CH:20]=[CH:19][C:15]([C:16](O)=[O:17])=[C:14]([F:21])[CH:13]=2)[N:9]=1)(=[O:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[BH4-].[Na+].O>O1CCCC1>[F:21][C:14]1[CH:13]=[C:12]([CH2:11][CH2:10][C:8]2[N:9]=[C:5]([NH:4][C:1](=[O:3])[CH3:2])[S:6][CH:7]=2)[CH:20]=[CH:19][C:15]=1[CH2:16][OH:17]

Participants

6

Reactant 4

HCID 962Water2×HCID 682631,1'-CarbonyldiimidazoleHCID 4311764Sodium borohydrideHCID 86649987HCID 86649987, compound

Product 1

HCID 86649988N-(4-{2-[3-fluoro-4-(hydroxymethyl)phenyl]ethyl}-1,3-thiazol-2-yl)acetamideYield 64.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of 4-{2-[2-(acetylamino)-1,3-thiazol-4-yl]ethyl}-2-fluorobenzoic acid (555.0 mg, 1.800 mmol) in anhydrous tetrahydrofuran (4 ml) was added 1,1′-carbonyldiimidazole (364.8 mg, 2.250 mmol), and the mixture was stirred at room temperature for 1.5 hr. The reaction mixture was added dropwise to a mixture of sodium borohydride (1.362 g, 36.0 mmol), tetrahydrofuran (36 ml) and water (9 ml), which had been cooled to −25° C. After stirring at not more than 0° C. for 1 hr, water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The combined organic layer was washed with 1M hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure, and a mixture of methanol (0.5 ml) and diisopropyl ether (15 ml) was added to the residue. The precipitate was collected by filtration and dried under reduced pressure to give N-(4-{2-[3-fluoro-4-(hydroxymethyl)phenyl]ethyl}-1,3-thiazol-2-yl)acetamide (342.8 mg, 1.165 mmol, yield 64.7%) as a white solid.

Workup

  1. temperaturehad been cooled to −25° C
  2. stirringAfter stirring at not more than 0° C. for 1 hr
  3. extractionthe mixture was extracted twice with ethyl acetate
  4. washThe combined organic layer was washed with 1M hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationThe organic layer was concentrated under reduced pressure
  7. additiona mixture of methanol (0.5 ml) and diisopropyl ether (15 ml)
  8. additionwas added to the residue
  9. filtrationThe precipitate was collected by filtration
  10. customdried under reduced pressure

Sources & evidence

ORD record
ord-8a60d50e5068412f904095e0dac39b3e
Source dataset
uspto-grants-2013_08
Patent number
US08507690B2

Reaction notes

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