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

HRID 1897327노트

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HRID 1897327 반응식
[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

참가 물질

8

반응물 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 4311764Sodium borohydrideHCID 234478853-(4-Fluoro-phenyl)-isoxazole-4-carboxylic acid

생성물 1

HCID 67158292[3-(4-Fluoro-phenyl)-isoxazol-4-yl]-methanol수율 54%

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회HCID 14798Sodium Hydroxide용매

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온도
-10 °C

실험 절차

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]+.

후처리

  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)

출처 및 근거

ORD 기록
ord-f96660d0250942fe84bd5e23416e09f7
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08518974B2

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