Benzyl chloroformate → 1-Boc-4-Cbz-amino-piperidine

HRID 369115Notes

Reaction equation

HRID 369115 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.Cl[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26]>C(Cl)Cl>[CH2:28]([O:27][C:25]([NH:1][CH:2]1[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]1)=[O:26])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 12682914-Amino-1-Boc-piperidine

Product 1

HCID 15143051-Boc-4-Cbz-amino-piperidineYield 96.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1.2 g (6.0 mmol) 4-amino-1-t-butoxycarbonylpiperidine from Step B in 40 mL of methylene chloride was added 3.15 mL (18 mmol) of DIPEA and 1.03 mL (7.2 mmol) of benzyl chloroformate while cooled in an ice bath. After 0.5 h the reaction was quenched with aqueous sodium carbonate and extracted three times with methylene chloride. The organic layers were each washed with a portion of brine, dried over sodium sulfate, combined and concentrated. The residue was purified by FCC eluting with 25% ethyl acetate/hexanes to afford 1.94 g of title compound. 1H NMR (400 MHz, CDCl3): δ 1.26 (m, 2H), 1.42 (s, 9H), 1.90 (br d, J=12, 2H), 2.90 (br t, 2H), 3.58 (m, 1H), 4.08 (m, 2H), 4.42 (br s, 1H), 5.09 (s, 2H), 7.33 (m, 5H).

Workup

  1. temperaturewhile cooled in an ice bath
  2. customAfter 0.5 h the reaction was quenched with aqueous sodium carbonate
  3. extractionextracted three times with methylene chloride
  4. washeach washed with a portion of brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by FCC
  8. washeluting with 25% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-3b9f01fed19f4baca387ce9636f88a2d
Source dataset
uspto-grants-2000_10
Patent number
US06136827

Reaction notes

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