Water → 4-(5-Chloro-2-methoxy-phenyl)-4-methoxy-piperidine-1-carboxylic acid tert-butyl ester

HRID 1361516

반응식

HRID 1361516 반응식
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][C:13]([C:17]2[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:18]=2[O:24][CH3:25])([OH:16])[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH3:26]I.O>CN(C=O)C>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][C:13]([C:17]2[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:18]=2[O:24][CH3:25])([O:16][CH3:26])[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4]

참가 물질

6

반응물 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 58772480Tert-butyl 4-(5-chloro-2-methoxyphenyl)-4-hydroxypiperidine-1-carboxylate

생성물 1

HCID 587725284-(5-Chloro-2-methoxy-phenyl)-4-methoxy-piperidine-1-carboxylic acid tert-butyl ester수율 73.6%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

To a suspension of NaH (0.7 g, 60% in mineral oil, 17.5 mol) in DMF (30 mL) was added dropwise a solution of 4-(5-chloro-2-methoxy-phenyl)-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester 5b (4.0 g, 11.7 mol) in DMF (10 mL) at 0° C. After being stirred at this temperature for 30 min, MeI (0.9 ml 0.0145 mol) was added dropwise. The reaction mixture was stirred at 0° C. for 30 min and then warmed to room temperature. Water (100 mL) was added and the mixture was extracted with ethyl acetate (100 mL×3). The combined organic layers were washed with water and brine, dried over Na2SO4, and concentrated to obtain crude 4-(5-chloro-2-methoxy-phenyl)-4-methoxy-piperidine-1-carboxylic acid tert-butyl ester 5c (3.8 g), which was used directly in next step.

후처리

  1. stirringThe reaction mixture was stirred at 0° C. for 30 min
  2. extractionthe mixture was extracted with ethyl acetate (100 mL×3)
  3. washThe combined organic layers were washed with water and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated

출처 및 근거

ORD 기록
ord-a6b773ef2bc24af8bdd976668daae82d
출처 데이터셋
uspto-grants-2011_02
특허 번호
US07880007B2

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