Citrate → tert-butyl (2S)-2-(3-fluoro-4-methylbenzoyl)pyrrolidine-1-carboxylate

HRID 1920777Notes

Reaction equation

HRID 1920777 reaction equation
CON(C)[C:4]([C@@H:6]1[CH2:10][CH2:9][CH2:8][N:7]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:5].Br[Mg][C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[C:23]([F:28])[CH:22]=1.C([O-])(=O)CC(CC([O-])=O)(C([O-])=O)O>O1CCCC1>[F:28][C:23]1[CH:22]=[C:21]([CH:26]=[CH:25][C:24]=1[CH3:27])[C:4]([C@@H:6]1[CH2:10][CH2:9][CH2:8][N:7]1[C:11]([O:13][C:14]([CH3:15])([CH3:16])[CH3:17])=[O:12])=[O:5]

Participants

5

Reactant 3

HCID 31348CitrateHCID 6882981,1-Dimethylethyl (2S)-2-[(methoxymethylamino)carbonyl]-1-pyrrolidinecarboxylateHCID 178426143HCID 178426143, compound

Product 1

HCID 58580634tert-butyl (2S)-2-(3-fluoro-4-methylbenzoyl)pyrrolidine-1-carboxylateYield 48%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of tert-butyl (2S)-2-[methoxy(methyl)carbamoyl]pyrrolidine-1-carboxylate (2.35 g, 9.10 mmol) in tetrahydrofuran (10 mL), 0.5 M solution of bromo(3-fluoro-4-methylphenyl)magnesium in tetrahydrofuran (20 mL, 10 mmol) was added dropwise under an argon atmosphere and ice cooling. Upon the completion of the dropwise addition, the mixture was stirred for 16 hours at room temperature, and then added with saturated aqueous citrate solution (40 mL). The mixture obtained was extracted with ethyl acetate (30 mL×3) and the organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (n-hexane/ethyl acetate=6/4) to give the title compound as a brown oily substance (1.35 g, yield 48%).

Workup

  1. additionUpon the completion of the dropwise addition
  2. customThe mixture obtained
  3. extractionwas extracted with ethyl acetate (30 mL×3)
  4. washwashed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customThe residue was purified by silica gel chromatography (n-hexane/ethyl acetate=6/4)

Sources & evidence

ORD record
ord-a0339c08c81b47bf84405c5e4feb8b18
Source dataset
uspto-grants-2012_05
Patent number
US08173631B2

Reaction notes

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