Triethylamine → [3-(4-Fluoro-phenyl)-isoxazol-4-yl]-methanol

HRID 83424Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13](O)=[O:14])=[CH:11][O:10][N:9]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.C(OC(Cl)=O)C.[BH4-].[Na+]>C1COCC1.O.[OH-].[Na+]>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:12]([CH2:13][OH:14])=[CH:11][O:10][N:9]=2)=[CH:6][CH:7]=1

Participants

Conditions

Temperature: -10 °C

Procedure

To a solution of 3-(4-fluoro-phenyl)-isoxazole-4-carboxylic acid (40 g, 193 mmol) in THF (400 mL) at −10° C. was added triethylamine (27.1 mL, 193 mmol) and then a solution of ethylchloroformate (18.8 mL, 193 mmol) in THF (120 mL) added keeping the temperature below −5° C. After 1 h the mixture was filtered and the filtrate cooled to −10° C. and a suspension of sodiumborohydride (19 g, 483 mmol) in water (120 mL) added over 15 minutes keeping the temperature below −5° C. The mixture was then allowed to warm up to room temperature over 2 h and diluted with aqueous sodium hydroxide (1 N, 700 mL) and extracted with tert-butylmethylether. The combined organic layers were then washed with water and brine, dried over sodium sulfate and evaporated. Purification by chromatography (SiO2, heptane:ethyl acetate=1:1) afforded the title product (20.1 g, 54%) which was obtained as white solid. MS: m/e=194.1 [M+H]+.

Workup

customthe temperature below −5° C
filtrationAfter 1 h the mixture was filtered
additionadded over 15 minutes
customthe temperature below −5° C
temperatureto warm up to room temperature over 2 h
extractionextracted with tert-butylmethylether
washThe combined organic layers were then washed with water and brine
dry with materialdried over sodium sulfate
customevaporated
customPurification by chromatography (SiO2, heptane:ethyl acetate=1:1)

Sources & evidence

ORD record: ord-42a989ace6c34cfd82e5e0bc441e967c
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846719B2

Reaction notes

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