Pyridine → Benzyl 2-(3-fluoro-4-(2-hydroxy-3-(methoxycarbonyl)phenylcarbamyl)phenyl)pyrrolidine-1-carboxylate

HRID 415157Notes

Reaction equation

HRID 415157 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[CH:27]=[CH:26][C:25]([CH:28]2[CH2:32][CH2:31][CH2:30][N:29]2[C:33]([O:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[O:34])=[CH:24][C:23]=1[F:43])=[O:21]>ClCCl>[F:43][C:23]1[CH:24]=[C:25]([CH:28]2[CH2:32][CH2:31][CH2:30][N:29]2[C:33]([O:35][CH2:36][C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)=[O:34])[CH:26]=[CH:27][C:22]=1[C:20](=[O:21])[NH:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[C:3]=1[OH:12]

Participants

5

Reactant 3

HCID 1049PyridineHCID 12782444Methyl 3-amino-2-hydroxybenzoateHCID 86633086Benzyl 2-(4-(chlorocarbonyl)-3-fluorophenyl)pyrrolidine-1-carboxylate

Product 1

HCID 66620560Benzyl 2-(3-fluoro-4-(2-hydroxy-3-(methoxycarbonyl)phenylcarbamyl)phenyl)pyrrolidine-1-carboxylateYield 81.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a stirred solution of methyl 3-amino-2-hydroxybenzoate (3.4 g, 20.4 mmol) and pyridine in anhydrous dichloromethane (35 mL) was added dropwise a solution of benzyl 2-(4-(chlorocarbonyl)-3-fluorophenyl)pyrrolidine-1-carboxylate (8.87 g, 24.5 mmol) in anhydrous dichloromethane (90 mL). After the addition, the mixture was stirred at room temperature overnight. The mixture was diluted with dichloromethane, washed with water, 1N HCl, brine, dried over anhydrous sodium sulfate, and concentrated, re-crystallized from ethyl acetate to give benzyl 2-(3-fluoro-4-(2-hydroxy-3-(methoxycarbonyl)phenylcarbamyl)phenyl)pyrrolidine-1-carboxylate as white solid (8.20 g, yield 68%). 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 1.77-1.87 (m, 3H), 2.33-2.37 (m, 1H), 3.55-3.58 (m, 1H), 3.64-3.70 (m, 1H), 3.83 (s, 3H), 4.86-5.07 (m, 3H), 6.65 (s, 1H), 6.92 (s, 1H), 7.19-7.39 (m, 6H), 7.48-7.51 (m, 1H), 7.82-7.84 (m, 1H), 8.25-8.30 (m, 1H), 9.86 (br s, 1H), 10.99 (br s, 1H); LC-MS (ESI) m/z: 493 (M+1)+.

Workup

  1. additionAfter the addition
  2. washwashed with water, 1N HCl, brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated
  5. customre-crystallized from ethyl acetate

Sources & evidence

ORD record
ord-3f59a818560847baa258653e1a6b5c5e
Source dataset
uspto-grants-2012_01
Patent number
US08088760B2

Reaction notes

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