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

HRID 1514675Notes

Reaction equation

HRID 1514675 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13](O)=[O:14])=[C:11](/[CH:16]=[CH:17]/[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[O:10][N:9]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.ClC(OCC)=O.[BH4-].[Na+].[OH-].[Na+]>C1COCC1.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:12]([CH2:13][OH:14])=[C:11](/[CH:16]=[CH:17]/[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[O:10][N:9]=2)=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 666438363-(4-Fluoro-phenyl)-5-((E)-styryl)-isoxazole-4-carboxylic acid

Product 1

HCID 66643905[3-(4-Fluoro-phenyl)-5-((E)-styryl)-isoxazol-4-yl]-methanolYield 63%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-(4-fluoro-phenyl)-5-((E)-styryl)-isoxazole-4-carboxylic acid (19.0 g, 61.4 mmol) and triethylamine (8.6 mL, 61.4 mmol) in THF (475 mL) was added at room temperature a solution of ethyl chloroformate (5.97 mL, 61.4 mmol) in THF (55 mL). After 1 h the triethylamine hydrochloride salt was filtered off and washed with a small amount of THF. The mixture was added to a solution of sodium borohydride (6.05 g, 154 mmol) and water (55 mL). After stirring overnight at room temperature aqueous sodium hydroxide solution (1 N, 180 mL) was added. Extraction with tert-butylmethylether, removal of the solvent by distillation and chromatography (silica, dichloromethane:methanol=1:0 to 95:5) afforded the title compound (11.4 g, 63%) as light yellow solid. MS: m/e=296.2 [M+H]+.

Workup

  1. filtrationAfter 1 h the triethylamine hydrochloride salt was filtered off
  2. washwashed with a small amount of THF
  3. additionwas added
  4. extractionExtraction
  5. customwith tert-butylmethylether, removal of the solvent
  6. distillationby distillation and chromatography (silica, dichloromethane:methanol=1:0 to 95:5)

Sources & evidence

ORD record
ord-44e2479081464319bd8b33ac1a73bfd8
Source dataset
uspto-grants-2012_07
Patent number
US08222246B2

Reaction notes

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