Sodium Bicarbonate → ethyl 2-((R)-1-((S)-2-(tert-butyldimethylsilyloxy)-2-(4-cyanophenyl)ethyl)piperidin-3-yl)acetate

HRID 1948496노트

반응식

HRID 1948496 반응식
Br[CH2:2][C@H:3]([C:12]1[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][CH:13]=1)[O:4][Si:5]([C:8]([CH3:11])([CH3:10])[CH3:9])([CH3:7])[CH3:6].C(=O)(O)[O-].[Na+].[NH:25]1[CH2:30][CH2:29][CH2:28][C@H:27]([CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:26]1>C1COCC1>[Si:5]([O:4][C@@H:3]([C:12]1[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][CH:13]=1)[CH2:2][N:25]1[CH2:30][CH2:29][CH2:28][C@H:27]([CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:26]1)([C:8]([CH3:11])([CH3:10])[CH3:9])([CH3:7])[CH3:6]

참가 물질

5

반응물 3

HCID 516892Sodium BicarbonateHCID 7161133ethyl 2-[(3R)-piperidin-3-yl]acetateHCID 66955431(S)-4-(2-bromo-1-(tert-butyldimethylsilyloxy)ethyl)benzonitrile

생성물 1

HCID 66955124ethyl 2-((R)-1-((S)-2-(tert-butyldimethylsilyloxy)-2-(4-cyanophenyl)ethyl)piperidin-3-yl)acetate수율 62.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a mixture of (S)-4-(2-bromo-1-(tert-butyldimethylsilyloxy)ethyl)benzonitrile (7 g, 20.57 mmol) and sodium bicarbonate (2.073 g, 24.68 mmol) in THF (100 mL) was added (R)-ethyl 2-(piperidin-3-yl)acetate (3.52 g, 20.57 mmol). The reaction was heated at reflux for 5 days and then cooled, filtered, and concentrated in vacuo. The crude product was purified on a silica gel cartridge eluting with methanol/dichloromethane gradient (0% for 5 minutes then 0-100% over 20 minutes) to afford 5.5 g of ethyl 2-((R)-1-((S)-2-(tert-butyldimethylsilyloxy)-2-(4-cyanophenyl)ethyl)piperidin-3-yl)acetate. MS (M+1)=431; HPLC RT=1.90 minutes. 1H NMR (400 MHz, CDCl3) δ ppm 7.61 (2H, d), 7.45 (2H, d), 4.76 (1H, m), 4.12 (2H, q), 2.75 (1H, m), 2.69 (1H, m), 2.52 (1H, dd), 2.33 (1H, dd), 2.18 (2H, m), 2.10 (1H, dt), 2.00 (1H, m), 1.88 (1H, tt), 1.72 (1H, m), 1.59 (2H, m), 1.25 (3H, t), 1.0 (1H, m), 0.89 (9H, s), 0.08 (3H, s), −0.07 (3H, s).

후처리

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 5 days
  3. temperaturecooled
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified on a silica gel cartridge
  7. washeluting with methanol/dichloromethane gradient (0% for 5 minutes

출처 및 근거

ORD 기록
ord-fa67c04bce894846a7a0e838f7ef2142
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08399451B2

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