Methyl iodide → (+/-)-(4R*,5R*)-5-ethoxycarbonyl-1-methyl-4-(4-methoxy-phenyl)pyrrolidin-2-one

HRID 1837976Notes

Reaction equation

HRID 1837976 reaction equation
[CH2:1]([O:3][C:4]([C@@H:6]1[N:10]([CH3:11])[C:9](=[O:12])[CH2:8][C@@H:7]1[C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1)=[O:5])[CH3:2].[C:20]([O-])([O-])=O.[Cs+].[Cs+].IC>CC(C)=O>[CH2:1]([O:3][C:4]([C@@H:6]1[N:10]([CH3:11])[C:9](=[O:12])[CH2:8][C@@H:7]1[C:13]1[CH:14]=[CH:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 59066485(+/-)-(4R*,5R*)-5-ethoxycarbonyl-1-methyl-4-(4-hydroxyphenyl)pyrrolidin-2-one

Product 1

HCID 59066500(+/-)-(4R*,5R*)-5-ethoxycarbonyl-1-methyl-4-(4-methoxy-phenyl)pyrrolidin-2-oneYield 93%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of (±)-(4R*,5R*)-5-ethoxycarbonyl-1-methyl-4-(4-hydroxyphenyl)pyrrolidin-2-one (prepared according to the procedure described for Intermediate W, 0.74 g, 2.81 mmol) in acetone (10 mL) was added Cs2CO3 (2.03 g, 5.62 mmol), followed by iodomethane (0.19 mL, 3.1 mmol). The reaction was stirred at room temperature for 72 h and filtered. The filtrate was concentrated under reduced pressure. The resulting oil was purified by flash chromatography (EtOAc) to yield (±)-(4R*,5R*)-5-ethoxycarbonyl-1-methyl-4-(4-methoxy-phenyl)pyrrolidin-2-one (0.72 g, 93%) as a white solid: 1H NMR (DMSO-d6) δ 0.73 (t, J=6.0 Hz, 3H), 2.44-2.71 (m, 5H), 3.56-3.78 (m, 5H), 3.88 (q, J=8.8 Hz, 1H), 4.42 (d, J=8.8 Hz, 1H), 6.82-6.87 (m, 2H), 7.11-7.16 (m, 2H).

Workup

  1. filtrationfiltered
  2. concentrationThe filtrate was concentrated under reduced pressure
  3. customThe resulting oil was purified by flash chromatography (EtOAc)

Sources & evidence

ORD record
ord-cc8c9a151d634b52a36cf392bd3beacb
Source dataset
uspto-grants-2004_08
Patent number
US06784167B2

Reaction notes

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