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

HRID 1948496Notes

Reaction equation

HRID 1948496 reaction equation
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]

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-fa67c04bce894846a7a0e838f7ef2142
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

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