Pyridine → Benzyl 2-(2-hydroxy-3-(methoxycarbonyl)phenylcarbamoyl)-2-methylpyrrolidine-1-carboxylate

HRID 415270Notes

Reaction equation

HRID 415270 reaction equation
[NH2:1][C:2]1[C:3]([OH:12])=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].N1C=CC=CC=1.Cl[C:20]([C:22]1([CH3:37])[CH2:26][CH2:25][CH2:24][N:23]1[C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28])=[O:21]>ClCCl>[OH:12][C:3]1[C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:9][CH:10]=[CH:11][C:2]=1[NH:1][C:20]([C:22]1([CH3:37])[CH2:26][CH2:25][CH2:24][N:23]1[C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28])=[O:21]

Participants

5

Reactant 3

HCID 1049PyridineHCID 12782444Methyl 3-amino-2-hydroxybenzoateHCID 86633083Benzyl 2-(chlorocarbonyl)-2-methylpyrrolidine-1-carboxylate

Product 1

HCID 66621011Benzyl 2-(2-hydroxy-3-(methoxycarbonyl)phenylcarbamoyl)-2-methylpyrrolidine-1-carboxylateYield 70.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of methyl 3-amino-2-hydroxybenzoate (0.576 g, 3.45 mmol) and pyridine (0.546 g, 6.9 mmol) in anhydrous dichloromethane (20 mL) was added drop wise a solution of benzyl 2-(chlorocarbonyl)-2-methylpyrrolidine-1-carboxylate (1.07 g, 3.8 mmol) in anhydrous dichloromethane (5 mL). After the addition, the mixture was stirred at room temperature overnight. Removed the solvents and purified by silica gel chromatography (petroleum ether/ethyl acetate=100:1 to 25:1) to obtain a yellow oil of benzyl 2-(2-hydroxy-3-(methoxycarbonyl)phenylcarbamoyl)-2-methylpyrrolidine-1-carboxylate (1 g, yield 66%). 1H-NMR (400 MHz, DMSO-d6): δ 1.53-1.58 (m, 3H), 1.88-1.91 (m, 3H), 1.28 (brs, 1H), 3.53-3.65 (m, 2H), 3.92 (s, 3H), 5.02-5.15 (m, 2H), 6.92-6.96 (m, 1H), 7.16-7.34 (m, 5H), 7.55-7.57 (d, J=7.8 Hz, 1H), 7.88-8.12 (m, 1H), 8.72-8.89 (d, 1H), 10.82 (s, 1H); LC-MS (ESI) m/z: 413 (M+1)+.

Workup

  1. additionAfter the addition
  2. customRemoved the solvents
  3. custompurified by silica gel chromatography (petroleum ether/ethyl acetate=100:1 to 25:1)

Sources & evidence

ORD record
ord-79135df163354cac9a245a063be8db28
Source dataset
uspto-grants-2012_01
Patent number
US08088760B2

Reaction notes

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