tert-Butanol → 4-Fluoro-4-(4-fluoro-benzoyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1961633노트

반응식

HRID 1961633 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:22])[C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(O)(C)C.C(O[K])(C)(C)C.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:44])(=O)=O)=CC=1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([F:44])([C:14](=[O:22])[C:15]2[CH:16]=[CH:17][C:18]([F:21])=[CH:19][CH:20]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

참가 물질

6

반응물 4

HCID 6386tert-ButanolHCID 588007N-Fluorobenzenesulfonimide3회HCID 7016484tert-butyl 4-(4-fluorobenzoyl)piperidine-1-carboxylateHCID 178418922HCID 178418922, 화합물3회

생성물 1

HCID 179792084-Fluoro-4-(4-fluoro-benzoyl)-piperidine-1-carboxylic acid tert-butyl ester수율 58%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

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온도
0 °C

실험 절차

4-(4-Fluoro-benzoyl)-piperidine-1-carboxylic acid tert-butyl ester in 0.5 mL of DMF was added to a solution at 0° C. containing 0.5 mL of tBuOH, (0.109 mg, 0.651 mmol) tBuOK and 2 mL of DMF. After 20 min stirring at 0° C., N-Fluorobenzenesulfonimide (0.246 g, 0.781 mmol) was added portionwise. The reaction was stirred at 0° C. during 45 min. and (0.55 g, 0.33 mmol) of tBuOK were added at 0° C. and 10 min later (0.123 g, 0.390 mmol) of N-Fluorobenzenesulfonimide. Each 0.5 h two more additions of (0.55 g, 0.33 mmol) tBuOK and (0.123 g, 0.390 mmol) N-Fluorobenzenesulfonimide were repited. 1 h later of the last addition the reaction was quenched with 4 mL of water and the DMF was removed under vacuum. The water was extracted with ethyl acetate and the combined organic phases were purified with column chromatography on silica using n-heptane-EtOAc (3:1). The product fractions were concentrated to give 0.122 g (0.375 mmol, 58% yield) of a yellow oil. MS (m/e): 326.1 (M+H+).

후처리

  1. stirringThe reaction was stirred at 0° C. during 45 min.
  2. addition1 h later of the last addition the reaction
  3. customwas quenched with 4 mL of water
  4. customthe DMF was removed under vacuum
  5. extractionThe water was extracted with ethyl acetate
  6. customthe combined organic phases were purified with column chromatography on silica
  7. concentrationThe product fractions were concentrated

출처 및 근거

ORD 기록
ord-bef2989722e743189c6bc411716684fc
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415350B2

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