Diisopropylethylamine → 1-Benzyl 2-methyl (2S)-piperidine-1,2-dicarboxylate

HRID 1826574Notes

Reaction equation

HRID 1826574 reaction equation
Cl.[CH3:2][O:3][C:4]([C@@H:6]1[CH2:11][CH2:10][CH2:9][CH2:8][NH:7]1)=[O:5].C(N(C(C)C)CC)(C)C.[CH2:21]([O:28][C:29](ON1C(=O)CCC1=O)=[O:30])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>ClCCl>[CH3:2][O:3][C:4]([C@@H:6]1[CH2:11][CH2:10][CH2:9][CH2:8][N:7]1[C:29]([O:28][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:30])=[O:5]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 83172Benzyl succinimido carbonateHCID 13246232methyl (2S)-piperidine-2-carboxylate hydrochloride

Product 1

HCID 450725361-Benzyl 2-methyl (2S)-piperidine-1,2-dicarboxylateYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred suspension of (S)-piperidine-2-carboxylic acid methyl ester hydrochloride salt (5.0 g, 27.8 mmol) in dichloromethane (DCM) (35 mL ) at 0° C. was added diisopropylethylamine (DIPEA) (10.1 mL, 58.4 mmol) followed by N-(benzyloxycarbonyloxy)succinimide (7.63 g, 30.6 mmol). The reaction mixture was allowed to warm to room temperature and stirred overnight. The residue was diluted with DCM and washed with 1.0-M HCl. The organic layer was washed with brine, dried(Na2SO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography (20% ethyl acetate in hexane) to afford the title compound as a pale yellow oil (7.72, 100%): 1H NMR (400 MHz, CD3OD) δ 1.19–1.88 (5H, m), 2.15–2.28 (1H, m), 2.91–3.12 (1H, m), 3.70–3.73 (3H, 2s), 4.00–4.07 (1H, m), 4.82–4.87 (1H, m), 5.03–5.21 (2H, m), 7.24–7.39 (5H, m); 13C NMR (100 MHz, CD3OD) δ 22.0, 22.1 (CH2), 26.0, 26.1 (CH2), 28.1 (CH2), 43.4, 43.5 (CH2), 53.1 (CH3), 56.2, 56.5 (CH), 68.8, 68.9 (CH2), 129.2 (CH), 129.5 (CH), 129.9 (CH), 138.4 (C), 167.0 (CO), 173.7 (CO).

Workup

  1. washwashed with 1.0-M HCl
  2. washThe organic layer was washed with brine, dried(Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography (20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-4eadfa30342947f38a8e382300321120
Source dataset
uspto-grants-2006_05
Patent number
US07053057B2

Reaction notes

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