Hydrochloric Acid → HCID 10061206, compound

HRID 229513Notes

Reaction equation

HRID 229513 reaction equation
[O:1]=[C:2]1[N:6]([C@@H:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH3:8])[CH2:5][C@H:4]([C:15]([O:17][CH3:18])=[O:16])[CH2:3]1.[CH3:19]I.[H-].[Na+].Cl>CN(C)C=O>[CH3:19][C:4]1([C:15]([O:17][CH3:18])=[O:16])[CH2:3][C:2](=[O:1])[N:6]([C@@H:7]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH3:8])[CH2:5]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 11637375(R)-methyl 5-oxo-1-((R)-1-phenylethyl)pyrrolidine-3-carboxylate

Product 1

HCID 10061206HCID 10061206, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl(3R)-5-oxo-1-[(R)-1-phenylethyl]pyrrolidin-3-yl-carboxylate (49.5 g, 200 mmol) and methyl iodide (37.4 mL, 600 mmol) in dimethylformamide (1 L), sodium hydride (in oil; content, 55%; 11.35 g: 260 mmol) was gradually added in 5 minutes at room temperature. After stirring at room temperature for 2 hours, methyl iodide (24.9 mL, 400 mmol) and sodium hydride (in oil; content, 55%; 6.11 g; 140 mmol) were further added, and the mixture was stirred for another 4 hours. The reaction mixture was added to 0.5N hydrochloric acid (1 L) in an ice bath, and extracted with ethyl acetate (2 L+1 L). The organic layers were combined and washed with water (1 L×2) and saturated aqueous solution of sodium chloride (1 L), and dried with anhydrous sodium sulfate. After removing the dessicating agent by filtration, the solvent was removed by distillation under reduced pressure. The thus obtained crude product was purified by silica gel column chromatography (hexane:ethyl acetate, 80:20→67:33→50:50→33:67) to obtain stereoisomers at position 3 of the title compound (stereoisomer A: 19.86 g (76.0 mmol, 38%) as a pale yellow oil, stereoisomer B: 20.22 g (77.4 mmol, 39%) as a pale yellow solid, and a mixture of stereoisomers A and B: 9.69 g (37.1 mmol, 19%) as a pale yellow oil.

Workup

  1. stirringthe mixture was stirred for another 4 hours
  2. extractionextracted with ethyl acetate (2 L+1 L)
  3. washwashed with water (1 L×2) and saturated aqueous solution of sodium chloride (1 L)
  4. dry with materialdried with anhydrous sodium sulfate
  5. customAfter removing the dessicating agent
  6. filtrationby filtration
  7. customthe solvent was removed by distillation under reduced pressure
  8. customThe thus obtained crude product
  9. customwas purified by silica gel column chromatography (hexane:ethyl acetate, 80:20→67:33→50:50→33:67)

Sources & evidence

ORD record
ord-648ad6999b814b77b21117217a7a62ef
Source dataset
uspto-grants-2009_07
Patent number
US07563805B2

Reaction notes

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