1-Methyl-4-piperidone → 1-methyl-4-(2-trityl-2,3-dihydro-1H-isoindol-5-yl)-piperidin-4-ol

HRID 41470

반응식

HRID 41470 반응식
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][N:6]([C:11]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH2:5]2.C([Li])CCC.[CH3:35][N:36]1[CH2:41][CH2:40][C:39](=[O:42])[CH2:38][CH2:37]1>C1COCC1>[CH3:35][N:36]1[CH2:41][CH2:40][C:39]([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[CH2:7][N:6]([C:11]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:5]3)([OH:42])[CH2:38][CH2:37]1

참가 물질

5

반응물 3

HCID 740491-Methyl-4-piperidoneHCID 592631135-Bromo-2-trityl-isoindolineHCID 178418339Butyllithium

생성물 1

HCID 592631371-methyl-4-(2-trityl-2,3-dihydro-1H-isoindol-5-yl)-piperidin-4-ol수율 57%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

Under nitrogen, a solution of 5-bromo-2-trityl-2,3-dihydro-1H-isoindole (2.03 g, 4.6 mmol) in THF (20 mL) was cooled to −78° C. n-Butyllithium solution (2.5M in hexanes, 2.0 mL, 5 mmol) was added over 5 minutes, then after 10 minutes, 1-methyl-4-piperidone was added dropwise. After a further hour, the cooling bath was removed and the reaction quenched with sodium bicarbonate solution. The mixture was extracted with ethyl acetate then the organic phase was washed with brine, dried (MgSO4) and concentrated. The residue was purified by flash chromatography on silica (gradient elution with 2M methanolic ammonia/dichloromethane, 0% to 5%) to afford 1-methyl-4-(2-trityl-2,3-dihydro-1H-isoindol-5-yl)-piperidin-4-ol as a pink foam (1.25 g, 57%). 1H NMR (MeOH-d4) 7.56 (6H, dd), 7.28 (6H, t), 7.25-7.21 (2H, m), 7.15 (3H, t), 7.03 (1H, d), 3.92 (2H, s), 3.91 (2H, s), 2.70 (2H, d), 2.53 (2H, td), 2.33 (3H, s), 2.06 (2H, td), 1.70 (2H, d). MS: [M+H]+ 475.

후처리

  1. additionwas added over 5 minutes
  2. waitAfter a further hour
  3. customthe cooling bath was removed
  4. customthe reaction quenched with sodium bicarbonate solution
  5. extractionThe mixture was extracted with ethyl acetate
  6. washthe organic phase was washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography on silica (gradient elution with 2M methanolic ammonia/dichloromethane, 0% to 5%)

출처 및 근거

ORD 기록
ord-b1c25a14c7cd45ebb31a29edfb6fe647
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08530469B2

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