Triethylamine → [3-(3,4-Difluoro-phenyl)-5-([E]-styryl)-isoxazol-4-yl]-methanol

HRID 1514705Notes

Reaction equation

HRID 1514705 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9]2[C:13]([C:14](O)=[O:15])=[C:12](/[CH:17]=[CH:18]/[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[O:11][N:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].C(N(CC)CC)C.ClC(OCC)=O.[BH4-].[Na+].[OH-].[Na+]>C1COCC1.O>[F:1][C:2]1[CH:3]=[C:4]([C:9]2[C:13]([CH2:14][OH:15])=[C:12](/[CH:17]=[CH:18]/[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[O:11][N:10]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 667181913-(3,4-Difluoro-phenyl)-5-([E]-styryl)-isoxazole-4-carboxylic acid

Product 1

HCID 66718189[3-(3,4-Difluoro-phenyl)-5-([E]-styryl)-isoxazol-4-yl]-methanolYield 73.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-(3,4-difluoro-phenyl)-5-([E]-styryl)-isoxazole-4-carboxylic acid (18 g, 55.0 mmol) and triethylamine (7.7 mL, 55.0 mmol) in THF (450 mL) was added at room temperature a solution of ethyl chloroformate (5.35 mL, 55.0 mmol) in THF (52 mL). After 1 h triethylamine hydrochloride salt was filtered off and washed with a small amount of THF. The solution was added to a solution of sodium borohydride (5.42 g, 138 mmol) in water (52 mL). The mixture was stirred overnight at room temperature. Sodium hydroxide solution (1 N, 180 mL) was added. Extraction with tert-butylmethylether and chromatography (silica, dichloromethane) afforded the title compound (12.6 g, 73%) as a light green solid. MS: m/e=314.2 [M+H]+.

Workup

  1. filtrationAfter 1 h triethylamine hydrochloride salt was filtered off
  2. washwashed with a small amount of THF
  3. extractionExtraction with tert-butylmethylether and chromatography (silica, dichloromethane)

Sources & evidence

ORD record
ord-6e3ac281b24a4500aa2c2c08801d68de
Source dataset
uspto-grants-2012_07
Patent number
US08222246B2

Reaction notes

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