5-Ethenyl-2-pyrrolidinone → (5S)-N-((2S)-2-((1,1-dimethylethyl)-dimethylsilyloxy)-3-phenylpropanoyl)-5-ethenylpyrrolidin-2-one

HRID 248188Notes

Reaction equation

HRID 248188 reaction equation
[H-].[Na+].[CH:3]([CH:5]1[NH:9][C:8](=[O:10])[CH2:7][CH2:6]1)=[CH2:4].[CH3:11][C:12]([Si:15]([CH3:29])([CH3:28])[O:16][C@@H:17]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:18](Cl)=[O:19])([CH3:14])[CH3:13]>O1CCCC1.C(Cl)Cl>[CH3:14][C:12]([Si:15]([CH3:28])([CH3:29])[O:16][C@@H:17]([CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[C:18]([N:9]1[C@H:5]([CH:3]=[CH2:4])[CH2:6][CH2:7][C:8]1=[O:10])=[O:19])([CH3:11])[CH3:13]

Participants

6

Reactant 3

HCID 241505-Ethenyl-2-pyrrolidinoneHCID 24758Sodium hydrideHCID 10780463(2S)-2-((1,1-Dimethylethyl)dimethylsilyloxy)-3-phenylpropanoyl chloride

Product 1

HCID 57291395(5S)-N-((2S)-2-((1,1-dimethylethyl)-dimethylsilyloxy)-3-phenylpropanoyl)-5-ethenylpyrrolidin-2-oneYield 46%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
25 °C

Procedure

To 60% sodium hydride (336 mg, 10 mmol, in mineral oil) in tetrahydrofuran (20 mL) at 0° C. was added dropwise a solution of 5-vinylpyrrolidin-2-one (1.0 g, 9.0 mmol) in tetrahydrofuran (10 mL) over a 5 min period. The cooling bath was removed and the solution was allowed to warm to 25° C. to ensure complete anion generation. To the anion at 25° C. was added dropwise a solution of (2S)-2-((1,1-dimethylethyl)dimethylsilyloxy)-3-phenylpropanoyl chloride (4, 2.98 g, 10 mmol) in tetrahydrofuran (10 mL) over a 5 min period. TLC indicated that the reaction was complete upon addition of the acid chloride (silica gel plates; hexane and ethyl acetate, 9:1). The solvent was removed by rotary evaporation affording a thick slug. The slug was dissolved in methylene chloride (75 mL) and washed with water (1×50 mL), a saturated aqueous sodium bicarbonate solution (1×50 mL) and dried (MgSO 4). Concentration and purification by flash chromatography on silica gel (EM 60, 0.040-0.063 partical size, 230-400 Mesh, column size: 4.5 cm diameter×15 cm length) using hexane and ethyl acetate (19:1) afforded 1.54 g (46%) of (5S)-N-((2S)-2-((1,1-dimethylethyl)-dimethylsilyloxy)-3-phenylpropanoyl)-5-ethenylpyrrolidin-2-one (5a) as a white crystalline material: mp 92°-93.5° C.; 1H NMR (CDCl3) δ-0.316 (s,3 H), -0.217 (s,3 H), 0.703 (s, 9 H), 1.94 (t, J=9.6 Hz, 1 H), 2.29 (p, J=11.7 Hz, 1 H), 2.50-2.75 (m, 3 H), 3.11 (d, J=12.8 Hz, 1 H), 4.97-5.13 (m, 1 H), 5.12-5.18 (m, 2 H), 5.45 (d, J=9.8 Hz, 1 H), 5.75-5.86 (m, 1 H); 13C NMR (CDCl3) δ175.1, 174.1, 137.9, 135.4, 130.0, 128.0, 126.4, 115.8, 74.2, 58.1, 41.2, 31.7, 25.5, 24.3, 18.1, -5.50, -5.76.

Workup

  1. customThe cooling bath was removed
  2. customThe solvent was removed by rotary evaporation
  3. customaffording a thick slug
  4. washwashed with water (1×50 mL)
  5. dry with materiala saturated aqueous sodium bicarbonate solution (1×50 mL) and dried (MgSO 4)
  6. concentrationConcentration and purification by flash chromatography on silica gel (EM 60, 0.040-0.063 partical size, 230-400 Mesh, column size: 4.5 cm diameter×15 cm length)

Sources & evidence

ORD record
ord-a36a9d59376d498b8b4629233912ffc4
Source dataset
uspto-grants-1993_05
Patent number
US05208345

Reaction notes

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