Benzyl chloroformate → Benzyl 3-(hydroxymethyl)piperidine-1-carboxylate

HRID 1660721Notes

Reaction equation

HRID 1660721 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:8][CH2:7][CH2:6][NH:5][CH2:4]1.[C:9](Cl)([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10]>C(Cl)Cl.CCN(CC)CC>[CH2:12]([O:11][C:9]([N:5]1[CH2:6][CH2:7][CH2:8][CH:3]([CH2:2][OH:1])[CH2:4]1)=[O:10])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

5

Reactant 2

HCID 10387Benzyl chloroformateHCID 107308Piperidin-3-ylmethanol

Product 1

HCID 2776577Benzyl 3-(hydroxymethyl)piperidine-1-carboxylateYield 94%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a stirred solution of 3-hydroxymethylpiperidine (1 g, 8.7 mmol) in CH2Cl2 (50 mL) and Et3N (1.12 mml) at 0° C. was added dropwise CbzCl (1.24 mL, 8.7 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was washed with brine, dried over Na2SO4, and concentrated. The residue was purified by chromatography with hexane-EtOAc (2:1) to give a colorless oil (2 g, 94%). 1H NMR (CDCl3) δ 7.35 (m, 5H), 5.12 (m, 2H), 4.20-3.60 (m, 2H), 3.47 (m, 2H), 3.20-2.20 (m, 3H), 1.82-1.10 (m, 5H); 13C NMR (CDCl3) δ 155.55, 136.73, 128.38, 127.85, 127.69, 66.96, 64.31, 46.74, 44.71, 38.01, 26.77, 24.05.

Workup

  1. washThe mixture was washed with brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customThe residue was purified by chromatography with hexane-EtOAc (2:1)

Sources & evidence

ORD record
ord-18922ce2ebfd408b8ad72472742843ff
Source dataset
uspto-grants-2011_10
Patent number
US08030300B2

Reaction notes

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