Triethylamine → 3-(4-Chloro-phenyl)-isoxazol-4-ylmethanol

HRID 1911652Notes

Reaction equation

HRID 1911652 reaction equation
[Cl: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+]>[Cl: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

8

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 4311764Sodium borohydrideHCID 289494543-(4-Chlorophenyl)-1,2-oxazole-4-carboxylic acid

Product 1

HCID 684443823-(4-Chloro-phenyl)-isoxazol-4-ylmethanolYield 46.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 14798Sodium HydroxideSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution of 3-(4-chloro-phenyl)-isoxazole-4-carboxylic acid (40.0 g, 178.9 mmol) in THF (370 mL) at −10° C. was added triethylamine (25.1 mL, 179 mmol) and then a solution of ethylchloroformate (17.4 mL, 179 mmol) in THF (111 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 (17.6 g, 447 mmol) in water (111 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, 648 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 (17.3 g, 46%) which was obtained as a light green solid. MS: m/e=210.1 [M+H]+.

Workup

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

Sources & evidence

ORD record
ord-3fde398adf8040bd8910109f5a851295
Source dataset
uspto-grants-2013_12
Patent number
US08604062B2

Reaction notes

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