Water → tert-Butyl 4-[(benzyloxy)methyl]-4-cyanopiperidine-1-carboxylate

HRID 1748307Notes

Reaction equation

HRID 1748307 reaction equation
[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)#[N:2].C[Si]([N-][Si](C)(C)C)(C)C.[K+].Cl[CH2:27][O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.O>C1COCC1.C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH2:29]([O:28][CH2:27][C:3]1([C:1]#[N:2])[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

8

Reactant 4

HCID 962WaterHCID 137983Benzyl chloromethyl etherHCID 1514443Tert-butyl 4-cyanopiperidine-1-carboxylateHCID 3251421Potassium bis(trimethylsilyl)amide

Product 1

HCID 53485182tert-Butyl 4-[(benzyloxy)methyl]-4-cyanopiperidine-1-carboxylateYield 48.3%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl 4-cyanopiperidine-1-carboxylate (4 g, 19 mmol) in THF (70 mL) cooled to 0° C. is added 0.5 M KHMDS (57 mL, 28.5 mmol) in toluene dropwise. The reaction mixture is warmed to room temperature and stirred for 1 h. Chloromethoxymethyl-benzene (4.46 g, 28.5 mmol) is added and the reaction mixture is stirred for another 1 h at room temperature. Water and ethyl acetate are added and the aqueous layer is separated and extracted with ethyl acetate (2×50 mL). The organic layers are combined, washed with brine, dried (Na2SO4) and concentrated to afford the title compound (3 g, 48.3%) as a light yellow liquid.

Workup

  1. stirringthe reaction mixture is stirred for another 1 h at room temperature
  2. customthe aqueous layer is separated
  3. extractionextracted with ethyl acetate (2×50 mL)
  4. washwashed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-ad56ba99a0b64e20a6b0a7125dfd4f2c
Source dataset
uspto-grants-2015_10
Patent number
US09150577B2

Reaction notes

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