Thionyl Chloride → Benzyl 4-(chlorocarbonyl)piperidine-1-carboxylate
Reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17]([OH:19])=O)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)([Cl:22])=O>ClCCl>[Cl:22][C:17]([CH:14]1[CH2:15][CH2:16][N:11]([C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:10])[CH2:12][CH2:13]1)=[O:19]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
To a stirred solution of 1-(benzyloxycarbonyl)piperidine-4-carboxylic acid (2.6 g, 10 mmol) in anhydrous dichloromethane (10 mL) was added dropwise thionyl chloride (10 mL) at 0° C. After the addition, the solution was stirred at room temperature overnight, and then the solvent was removed in vacuum to give benzyl 4-(chlorocarbonyl)piperidine-1-carboxylate. Then it was added to a solution of ethyl 3-amino-2-hydroxybenzoate (1.34 g, 8 mmol) and triethylamine (3 g, 30 mmol) in anhydrous dichloromethane (20 mL) at 0° C. After the addition, the mixture was stirred at room temperature overnight. The mixture was diluted with dichloromethane, washed with water (30 mL×3), brine (30 mL), dried over anhydrous sodium sulfate, and concentrated to give a crude product. The crude product was purified by chromatography (silica gel, petroleum ether/ethyl acetate=20:1 to 2:1) to give benzyl 4-(2-hydroxy-3-(methoxycarbonyl)phenylcarbamoyl)piperidine-1-carboxylate (2.63 g, yield 80%). 1H-NMR (400 MHz, CDCl3) δ (ppm): 1.46-1.56 (m, 2H), 1.79-1.82 (d, J=11.6 Hz, 2H), 2.75-2.87 (m, 3H), 3.92 (s, 3H), 4.04-4.07 (d, J=11.2 Hz, 2H), 5.08 (s, 2H), 6.90-6.94 (t, J=8 Hz, 1H), 7.30-7.40 (m, 5H), 7.54-7.56 (m, 1H), 8.09-8.11 (d, J=7.2 Hz, 1H), 9.34 (s, 1H), 10.99 (brs, 1H); LC-MS (ESI) m/z: 413 (M+1)+.
Workup
- additionAfter the addition
- customthe solvent was removed in vacuum
Sources & evidence
- ORD record
- ord-f6a43430e76c4c9d8661b64e0e37b745
- Source dataset
- uspto-grants-2012_01
- Patent number
- US08088760B2
Reaction notes
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