Ethyl Acetate → tert-Butyl 4-[(3R*,4S*)-3-[2-(tert-butoxy)-2-oxoethyl]-1-{[2-chloro-6-(trifluoromethyl)phenyl]methyl}-4-methylpyrrolidin-3-amido]piperidine-1-carboxylate

HRID 446007Notes

Reaction equation

HRID 446007 reaction equation
Br[CH2:2][C:3]1[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][CH:6]=[CH:5][C:4]=1[Cl:13].C(=O)([O-])[O-].[K+].[K+].[C:20]([O:24][C:25](=[O:49])[CH2:26][C@@:27]1([C:33]([NH:35][CH:36]2[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][CH2:37]2)=[O:34])[C@H:31]([CH3:32])[CH2:30][NH:29][CH2:28]1)([CH3:23])([CH3:22])[CH3:21].C(OCC)(=O)C>CN(C)C=O>[C:20]([O:24][C:25](=[O:49])[CH2:26][C@@:27]1([C:33]([NH:35][CH:36]2[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][CH2:37]2)=[O:34])[C@H:31]([CH3:32])[CH2:30][N:29]([CH2:2][C:3]2[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][CH:6]=[CH:5][C:4]=2[Cl:13])[CH2:28]1)([CH3:23])([CH3:21])[CH3:22]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 177506812-(Bromomethyl)-1-chloro-3-(trifluoromethyl)benzeneHCID 71293654tert-Butyl 4-[(3R*,4S*)-3-[2-(tert-butoxy)-2-oxoethyl]-4-methylpyrrolidin-3-amido]piperidine-1-carboxylate

Product 1

HCID 71293630tert-Butyl 4-[(3R*,4S*)-3-[2-(tert-butoxy)-2-oxoethyl]-1-{[2-chloro-6-(trifluoromethyl)phenyl]methyl}-4-methylpyrrolidin-3-amido]piperidine-1-carboxylateYield 63.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

2-(Bromomethyl)-1-chloro-3-(trifluoromethyl)benzene (443 mg, 1.62 mmol) and potassium carbonate (244 mg) were added to a solution of tert-butyl 4-[(3R*,4S*)-3-[2-(tert-butoxy)-2-oxoethyl]-4-methylpyrrolidin-3-amido]piperidine-1-carboxylate obtained in Example 3b (345 mg, 0.811 mmol) in N,N-dimethylformamide (dehydrated) (10 mL), which was stirred at 45° C. for six hours and at 40° C. for two days. Ethyl acetate was added to the reaction liquid, which was washed with a 1N aqueous sodium hydroxide solution and brine. This was dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (elution solvent: heptane/ethyl acetate) to give the title compound (320 mg, yield: 63.8%).

Workup

  1. washwas washed with a 1N aqueous sodium hydroxide solution and brine
  2. dry with materialThis was dried over anhydrous magnesium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by silica gel column chromatography (elution solvent: heptane/ethyl acetate)

Sources & evidence

ORD record
ord-67fc767e9d8b4b46b40454ad4e514ff8
Source dataset
uspto-grants-2013_07
Patent number
US08476301B2

Reaction notes

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