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

HRID 1948496ノート

反応式

HRID 1948496 の反応式
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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-fa67c04bce894846a7a0e838f7ef2142
出典データセット
uspto-grants-2013_03
特許番号
US08399451B2

反応ノート

読み込み中…