Potassium Carbonate → 4-{(S)-2-[4-(4-Chloro-benzyl)-phenoxymethyl]-pyrrolidin-1-yl}-butyric acid methyl ester

HRID 1909637Notes

Reaction equation

HRID 1909637 reaction equation
Cl.[Cl:2][C:3]1[CH:22]=[CH:21][C:6]([CH2:7][C:8]2[CH:20]=[CH:19][C:11]([O:12][CH2:13][C@@H:14]3[CH2:18][CH2:17][CH2:16][NH:15]3)=[CH:10][CH:9]=2)=[CH:5][CH:4]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:30][CH2:31][CH2:32][C:33]([O:35][CH3:36])=[O:34]>CN(C=O)C.O.C(OCC)(=O)C>[CH3:36][O:35][C:33](=[O:34])[CH2:32][CH2:31][CH2:30][N:15]1[CH2:16][CH2:17][CH2:18][C@H:14]1[CH2:13][O:12][C:11]1[CH:19]=[CH:20][C:8]([CH2:7][C:6]2[CH:21]=[CH:22][C:3]([Cl:2])=[CH:4][CH:5]=2)=[CH:9][CH:10]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 107604Methyl 4-bromobutyrateHCID 68998035(S)-2-[4-(4-Chloro-benzyl)-phenoxymethyl]-pyrrolidine hydrochloride

Product 1

HCID 690016424-{(S)-2-[4-(4-Chloro-benzyl)-phenoxymethyl]-pyrrolidin-1-yl}-butyric acid methyl esterYield 69%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the product from step 2 (1.50 g, 4.43 mmol) in DMF (20 mL) was added potassium carbonate (1.23 g, 8.90 mmol) and methyl 4-bromobutyrate (0.64 mL, 5.56 mmol). The resulting suspension was stirred at ambient temperature overnight. The reaction mixture diluted with water and ethyl acetate. The crude residue was extracted into ethyl acetate. The organic portion was washed with water, washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude product was purified by silica gel flash chromatography using hexane/EtOAc (gradient system) to give the title compound (1.22 g, 69%) as a yellow oil.

Workup

  1. extractionThe crude residue was extracted into ethyl acetate
  2. washThe organic portion was washed with water
  3. washwashed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-7b0a851d2c7046e981bce3cdde5c82ad
Source dataset
uspto-grants-2013_12
Patent number
US08598359B2

Reaction notes

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