2-[(3,4-Dichloro-5-fluoro-phenyl)-hydroxy-methyl]-2-propyl-pyrrolidine-1-carboxylic acid tert-butyl ester → 2-(3,4-Dichloro-5-fluoro-benzoyl)-2-propyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 661553Notes

Reaction equation

HRID 661553 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C:9]1([CH:16]([C:18]1[CH:23]=[C:22]([F:24])[C:21]([Cl:25])=[C:20]([Cl:26])[CH:19]=1)[OH:17])[CH2:13][CH2:14][CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C:9]1([C:16](=[O:17])[C:18]1[CH:23]=[C:22]([F:24])[C:21]([Cl:25])=[C:20]([Cl:26])[CH:19]=1)[CH2:13][CH2:14][CH3:15])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

3

Reactant 1

HCID 666880302-[(3,4-Dichloro-5-fluoro-phenyl)-hydroxy-methyl]-2-propyl-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 666873182-(3,4-Dichloro-5-fluoro-benzoyl)-2-propyl-pyrrolidine-1-carboxylic acid tert-butyl esterYield 68%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 2-[(3,4-dichloro-5-fluoro-phenyl)-hydroxy-methyl]-2-propyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.533 g, 1.31 mmol) in DCM (20 mL) at 0° C. under nitrogen was added DMP (0.557 g, 1.55 mmol) in a single portion. The reaction mixture was warmed to ambient temperature and stirred for 90 minutes. A second portion of DMP (0.110 g, 0.26 mmol) was added, and the reaction mixture was stirred for 30 minutes, then diluted with DCM, washed with 1 N NaOH, brine (20 mL), dried (MgSO4), filtered and concentrated in vacuo to a clear colourless oil (0.55 g). Purification by chromatography (silica, 5-20% EtOAc in hexanes) gave 2-(3,4-dichloro-5-fluoro-benzoyl)-2-propyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.358 g, 0.886 mmol, 68%) as a clear colourless gum.

Workup

  1. additionA second portion of DMP (0.110 g, 0.26 mmol) was added
  2. stirringthe reaction mixture was stirred for 30 minutes
  3. washwashed with 1 N NaOH, brine (20 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo to a clear colourless oil (0.55 g)
  7. customPurification by chromatography (silica, 5-20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-0af4123e634c4ac393b9bd9d3cf47b95
Source dataset
uspto-grants-2011_12
Patent number
US08084623B2

Reaction notes

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