Water → (5S)-N-((2S)-2-(3,5-di-t-butylphenyloxy)propanoyl)-5-ethenylpyrrolidin-2-one

HRID 248193Notes

Reaction equation

HRID 248193 reaction equation
[H-].[Na+].[CH:3]([CH:5]1[NH:9][C:8](=[O:10])[CH2:7][CH2:6]1)=[CH2:4].[C:11]([C:15]1[CH:16]=[C:17]([O:25][C@H:26]([CH3:30])[C:27](Cl)=[O:28])[CH:18]=[C:19]([C:21]([CH3:24])([CH3:23])[CH3:22])[CH:20]=1)([CH3:14])([CH3:13])[CH3:12].O>C1(C)C=CC=CC=1>[C:11]([C:15]1[CH:16]=[C:17]([O:25][C@@H:26]([CH3:30])[C:27]([N:9]2[C@H:5]([CH:3]=[CH2:4])[CH2:6][CH2:7][C:8]2=[O:10])=[O:28])[CH:18]=[C:19]([C:21]([CH3:23])([CH3:22])[CH3:24])[CH:20]=1)([CH3:12])([CH3:13])[CH3:14]

Participants

6

Reactant 4

HCID 962WaterHCID 241505-Ethenyl-2-pyrrolidinoneHCID 24758Sodium hydrideHCID 18651689(2R)-2-(3,5-Di-t-butylphenyloxy)propanoyl chloride

Product 1

HCID 57281788(5S)-N-((2S)-2-(3,5-di-t-butylphenyloxy)propanoyl)-5-ethenylpyrrolidin-2-oneYield 49.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Conditions

Temperature
25 °C

Procedure

To 60% sodium hydride (336 mg, 10 mmol) in toluene (20 mL) at 0° C. was added dropwise a solution of 5-vinylpyrrolidin-2-one (1.0 g, 9.0 mmol) in toluene (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 generation of the anion. To the anion at 25° C. was added dropwise a solution of (2R)-2-(3,5-di-t-butylphenyloxy)propanoyl chloride (11, 3.20 g, 9.8 mmol) in toluene (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, 2:1). Water (60 mL) was added to the reaction mixture and the phases were separated. The aqueous phase was extracted with ethylene chloride (1×40 mL). The combined organic phases were washed with a saturated aqeous sodium bicarbonate solution (1×70 mL) and dried (MgSO4). Concentration and purification by flash chromatography on silica gel (EM silica gel 60, 0.040-0.063 partical size, 230-400 Mesh, column size: 6.5 cm diameter×18 cm length) using hexane and ethyl acetate (19:1) afforded 1.65 g (46%) of (5S)-N-((2S)-2-(3,5 -di-t-butylphenyloxy)propanoyl)-5-ethenylpyrrolidin-2-one (15a) as an oil: 1H NMR (CDCl3) δ1.20 (s, 18 H), 1.60-1.62 (d, 3 H), 1.92-2.04 (m, 1 H), 2.21-2.32 (m, 1 H), 2.52-2.80 (m, 2 H), 4.9-4.96 (q, 1 H), 5.11-5.21 (m, 2 H), 5.77-5.88 (m, 1 H), 5.98-6.04 (q, 1 H), 6.71 (s, 2 H), 7.00 (s, 1 H); 13C NMR (CDCl3) δ175.2, 172.7, 157.1, 152.1, 135.2, 115.9, 115.6, 109.6, 72.3, 58.0, 34.9, 31.6, 31.4, 24.4, 18.1; IR (neat) 2966 (vs), 1740 (vs), 1715 (vs), 1593 (s), 1380 (s), 1229 (vs), 706 (w) cm-1.

Workup

  1. customThe cooling bath was removed
  2. customthe phases were separated
  3. extractionThe aqueous phase was extracted with ethylene chloride (1×40 mL)
  4. washThe combined organic phases were washed with a saturated aqeous sodium bicarbonate solution (1×70 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationConcentration and purification by flash chromatography on silica gel (EM silica gel 60, 0.040-0.063 partical size, 230-400 Mesh, column size: 6.5 cm diameter×18 cm length)

Sources & evidence

ORD record
ord-50e7429cfd994ec5ac38c9e4da77034b
Source dataset
uspto-grants-1993_05
Patent number
US05208345

Reaction notes

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