1-Methyl-4-piperidone → 5-(4-Hydroxy-1-methyl-piperidin-4-yl)-1,3-dihydroisoindole-2-carboxylic acid tert-butyl ester

HRID 41438

반응식

HRID 41438 반응식
C([Li])CCC.[C:6]([O:10][C:11]([N:13]1[CH2:21][C:20]2[C:15](=[CH:16][CH:17]=[C:18](Br)[CH:19]=2)[CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7].[CH3:23][N:24]1[CH2:29][CH2:28][C:27](=[O:30])[CH2:26][CH2:25]1>C1COCC1>[C:6]([O:10][C:11]([N:13]1[CH2:21][C:20]2[C:15](=[CH:16][CH:17]=[C:18]([C:27]3([OH:30])[CH2:28][CH2:29][N:24]([CH3:23])[CH2:25][CH2:26]3)[CH:19]=2)[CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7]

참가 물질

5

반응물 3

HCID 740491-Methyl-4-piperidoneHCID 16102683N-Boc-5-bromoisoindolineHCID 178418339Butyllithium

생성물 1

HCID 666723445-(4-Hydroxy-1-methyl-piperidin-4-yl)-1,3-dihydroisoindole-2-carboxylic acid tert-butyl ester

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

0.69 ml of n-Butyl lithium (2.5M solution in hexane) was added dropwise to a stirred solution of 5-bromo-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (429 mg; 1.44 mmol) in anhydrous THF (10 ml) at −78° C. under an atmosphere of nitrogen. The reaction was stirred for 50 minutes then 1-methyl-4-piperidone (212 μl; 1.2 equiv.) was added and stirred at −78° C. for a further 60 minutes then warmed to room temperature. The reaction was quenched with saturated ammonium chloride solution then extracted with EtOAc. The EtOAc layer was washed with saturated NaHCO3, brine, dried (MgSO4) and evaporated. Purification by flash column chromatography on SiO2, gradient elution from 0% to 10% 2M methanolic ammonia/DCM gave 111 mg of 5-(4-hydroxy-1-methyl-piperidin-4-yl)-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester as a colourless oil.

후처리

  1. stirringstirred at −78° C. for a further 60 minutes
  2. customThe reaction was quenched with saturated ammonium chloride solution
  3. extractionthen extracted with EtOAc
  4. washThe EtOAc layer was washed with saturated NaHCO3, brine
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customPurification by flash column chromatography
  8. washon SiO2, gradient elution from 0% to 10% 2M methanolic ammonia/DCM

출처 및 근거

ORD 기록
ord-8d39de1b14494e5d9b850af30ac4c7a1
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08530469B2

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