Triethylamine → 1-(2-Chloro-phenylcarbamoyl)-3-(4'-fluoro-biphenyl-4-yloxymethyl)-pyrrolidine-3-carboxylic acid ethyl ester

HRID 2060293Notes

Reaction equation

HRID 2060293 reaction equation
C(N(CC)CC)C.[CH2:8]([O:10][C:11]([C:13]1([CH2:18][O:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)=[CH:22][CH:21]=2)[CH2:17][CH2:16][NH:15][CH2:14]1)=[O:12])[CH3:9].[Cl:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[N:40]=[C:41]=[O:42]>ClCCl>[CH2:8]([O:10][C:11]([C:13]1([CH2:18][O:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=3)=[CH:22][CH:21]=2)[CH2:17][CH2:16][N:15]([C:41](=[O:42])[NH:40][C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=2[Cl:33])[CH2:14]1)=[O:12])[CH3:9]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 76833Chlorophenyl isocyanateHCID 593221953-(4'-Fluoro-biphenyl-4-yloxymethyl)-pyrrolidine-3-carboxylic acid ethyl ester

Product 1

HCID 593221711-(2-Chloro-phenylcarbamoyl)-3-(4'-fluoro-biphenyl-4-yloxymethyl)-pyrrolidine-3-carboxylic acid ethyl esterYield 91.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Triethylamine (0.23 mL, 1.67 mmol) was added to a stirred solution of 3-(4′-fluoro-biphenyl-4-yloxymethyl)-pyrrolidine-3-carboxylic acid ethyl ester (see Preparation 65) (185 mg, 0.54 mmol) in dichloromethane (10 mL) and the resulting mixture cooled to 0° C. 2-Chloro phenyl isocyanate (0.065 mL, 0.54 mmol) was added and the reaction mixture stirred at room temperature for 16 hours. The mixture was partitioned between water (25 mL) and dichloromethane (25 mL). The organic layer was separated, washed brine (25 mL), dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with 25% ethyl acetate in hexane to afford the title compound as a colourless liquid (245 mg, 91%).

Workup

  1. customThe mixture was partitioned between water (25 mL) and dichloromethane (25 mL)
  2. customThe organic layer was separated
  3. washwashed brine (25 mL)
  4. dry with materialdried over magnesium sulphate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography on silica gel
  7. washeluting with 25% ethyl acetate in hexane

Sources & evidence

ORD record
ord-ce571c14454445968747c3253c9e4aa7
Source dataset
uspto-grants-2012_10
Patent number
US08278343B2

Reaction notes

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