Cyclohexanone → HCID 67343263, compound

HRID 1825853Notes

Reaction equation

HRID 1825853 reaction equation
[NH2:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:3]1.[C:17]1(=O)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.C([BH3-])#N.[Na+]>CO>[CH2:10]([O:9][C:7]([N:4]1[CH2:5][CH2:6][C@H:2]([NH:1][CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[CH2:3]1)=[O:8])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 7967CyclohexanoneHCID 1519355(S)-1-Cbz-3-AminopyrrolidineHCID 5003444Sodium cyanoborohydride

Product 1

HCID 67343263HCID 67343263, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of (3S)-3-amino-pyrrolidine-1-carboxylic acid, benzyl ester (4.40 g, 20 mmol) in methanol (120 mL) was added cyclohexanone (2.75 g, 28 mmol) followed by sodium cyanoborohydride (1.50 g, 24 mmol) at room temprerature. After 3 h, the reaction mixture was concentrated, diluted with dichloromethane (200 mL), washed with aqueous sodium bicarbonate (100 mL), 1 N sodium hydroxide (50 mL), brine (50 mL) and dried (Na2SO4). The crude was purified by flash chromatography using 5% methanol in dichloromethane to give (3S)-3-cyclohexylamino-pyrrolidine-1-carboxylic acid benzyl ester in 73% yield. 1H NMR (300 MHz, CDCl3): in δ 7.36–7.26 (m, 5H), 5.11 (s, 2H), 3.65–3.35 (m, 4H), 3.1–2.95 (m, 1H), 2.5–2.38 (m, 1H), 2.11–1.98 (m, 1H), 1.92–1.54 (m, 5H), 1.31–0.95 (m, 6H); 13C NMR (300 MHz, CDCl3): in δ 154.9, 137.1, 128.4, 127.8, 66.7, 55.0, 54.6, 53.8, 52.6, 44.7, 44.3, 34.1, 32.8, 32.0, 26.1, 25.1; MS (ESI+), 303 (M+H); Rf=1.16.

Workup

  1. concentrationthe reaction mixture was concentrated
  2. additiondiluted with dichloromethane (200 mL)
  3. washwashed with aqueous sodium bicarbonate (100 mL), 1 N sodium hydroxide (50 mL), brine (50 mL)
  4. dry with materialdried (Na2SO4)
  5. customThe crude was purified by flash chromatography

Sources & evidence

ORD record
ord-54fd923280c44ee7bbef11dc4b5ba12c
Source dataset
uspto-grants-2006_05
Patent number
US07049323B2

Reaction notes

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