Tetrahydrofuran → Benzyl 4-(4-(tert-butyldimethylsilyloxy)butyl)-4-cyanopiperidine-1-carboxylate

HRID 597842

Reaction equation

HRID 597842 reaction equation
[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:5][CH2:4]1)#[N:2].CCCC.I[Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH2:41]1[CH2:45][O:44][CH2:43][CH2:42]1>>[Si:24]([O:44][CH2:43][CH2:42][CH2:41][CH2:45][C:3]1([C:1]#[N:2])[CH2:8][CH2:7][N:6]([C:9]([O:11][CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[O:10])[CH2:5][CH2:4]1)([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 2733832Lithium HexamethyldisilazideHCID 22028286Benzyl 4-cyanopiperidine-1-carboxylateHCID 86616696HCID 86616696, compound

Product 1

HCID 67270654Benzyl 4-(4-(tert-butyldimethylsilyloxy)butyl)-4-cyanopiperidine-1-carboxylateYield 67%

Procedure

To a stirred solution of benzyl 4-cyanopiperidine-1-carboxylate (10 g, 41 mmol) and iodo-tert-butyldimethylsilane butane (12.6 mL, 49 mmol) in THF (80 mL) cooled to −78° C. was added LiHMDS (50 mL, 50 mmol, 1M in THF) dropwise over 30 min. The resulting mixture was stirred while gradually warming to room temperature for 18 h. After quenching with water, the organic phase was diluted with EtOAc and washed with water, brine and dried (Na2SO4). After concentration, the residue was purified by flash chromatography (10% to 20% EtOAc/hexane) to give the title compound as yellow oil (11.88 g, 67% yield). 1H NMR (300 MHz, CDCl3) δ: 7.34-7.28 (5H, m), 5.09 (2H, s), 4.17 (2H, bs), 3.59 (2H, t, J=5.3 Hz), 3.07 (2H, bs), 1.89 (2H, d, J=13.2 Hz), 1.53 (6H, bs), 1.43-1.34 (2H, m), 0.85 (9H, s), 0.01 (6H, s). LCMS (M+H): 431.20.

Workup

  1. customAfter quenching with water
  2. additionthe organic phase was diluted with EtOAc
  3. washwashed with water, brine
  4. dry with materialdried (Na2SO4)
  5. concentrationAfter concentration
  6. customthe residue was purified by flash chromatography (10% to 20% EtOAc/hexane)

Sources & evidence

ORD record
ord-f009d28e78c04276a7da1ea5be3ef8c9
Source dataset
uspto-grants-2011_03
Patent number
US07897593B2

Linked notes

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