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

HRID 2060298Notes

Reaction equation

HRID 2060298 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].[CH:33]1([C:36](Cl)=[O:37])[CH2:35][CH2:34]1>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:36]([CH:33]2[CH2:35][CH2:34]2)=[O:37])[CH2:14]1)=[O:12])[CH3:9]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 77637Cyclopropanecarbonyl chlorideHCID 593221953-(4'-Fluoro-biphenyl-4-yloxymethyl)-pyrrolidine-3-carboxylic acid ethyl ester

Product 1

HCID 593222131-Cyclopropanecarbonyl-3-(4'-fluoro-biphenyl-4-yloxymethyl)-pyrrolidine-3-carboxylic acid ethyl esterYield 85.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Triethylamine (0.37 mL, 2.7 mmol) was added to a stirred solution of 3-(4′-fluoro-biphenyl-4-yloxymethyl)-pyrrolidine-3-carboxylic acid ethyl ester (see Preparation 65) (300 mg, 0.87 mmol) in dichloromethane (10 mL) and the resulting mixture cooled to 0° C. Cyclopropanecarbonyl chloride (0.08 mL, 0.87 mmol) was added and the reaction mixture stirred at room temperature for 16 hours. The mixture was partitioned between water (50 mL) and dichloromethane (50 mL). The organic layer was separated, washed brine (50 mL), dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with 15% ethyl acetate in hexane to afford the title compound as a pale yellow solid (305 mg, 85%).

Workup

  1. customThe mixture was partitioned between water (50 mL) and dichloromethane (50 mL)
  2. customThe organic layer was separated
  3. washwashed brine (50 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 15% ethyl acetate in hexane

Sources & evidence

ORD record
ord-c39a4859a5354c8ca738f6239e4ed3ad
Source dataset
uspto-grants-2012_10
Patent number
US08278343B2

Reaction notes

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