Water → (5S)-N-((2R)-2-(3,5-di-t-butyl-4-hydroxyphenyl)thiopropanoyl)-5-ethenylpyrrolidin-2-one

HRID 248203Notes

Reaction equation

HRID 248203 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]([S:26][C@H:27]([CH3:31])[C:28](Cl)=[O:29])[CH:18]=[C:19]([C:22]([CH3:25])([CH3:24])[CH3:23])[C:20]=1[OH:21])([CH3:14])([CH3:13])[CH3:12].O>C1(C)C=CC=CC=1>[C:22]([C:19]1[CH:18]=[C:17]([S:26][C@H:27]([CH3:31])[C:28]([N:9]2[C@H:5]([CH:3]=[CH2:4])[CH2:6][CH2:7][C:8]2=[O:10])=[O:29])[CH:16]=[C:15]([C:11]([CH3:13])([CH3:12])[CH3:14])[C:20]=1[OH:21])([CH3:23])([CH3:24])[CH3:25]

Participants

6

Reactant 4

HCID 962WaterHCID 241505-Ethenyl-2-pyrrolidinoneHCID 24758Sodium hydrideHCID 86746807(2R)-2-(3,5-Di-t-butyl-4-hydroxyphenyl)thiopropanoyl Chloride

Product 1

HCID 86746806(5S)-N-((2R)-2-(3,5-di-t-butyl-4-hydroxyphenyl)thiopropanoyl)-5-ethenylpyrrolidin-2-oneYield 32%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Procedure

To a solution of 60% sodium hydride (665 mg, 19.0 mmol) and toluene (40 mL) at 0° C. was added dropwise a solution of 5-vinylpyrrolidin-2-one (2.0 g, 18.0 mmol) in toluene (20 mL) over a 30 min period. The cooling bath was removed and the solution was allowed to warm to room temperature and stir there for a 30 min period to ensure complete anion generation. To the anion at 25° C. was added dropwise a solution of (2R)-2-(3,5-di-t-butyl-4-hydroxyphenyl)thiopropanoyl chloride (29, 6.21 g, 19.0 mmol) in toluene (20 mL) over a 20 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 (100 mL) was added to the reaction and the phases were separated. The aqueous phase was extracted with t-butyl methyl ether (2×100 mL). The combined organic phases were washed with a saturated aqueous sodium bicarbonate solution (1×250 mL) and dried (MgSO4). 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×24 cm length) using hexane and ethyl acetate (10:1) afforded 2.32 g (32%) of (5S)-N-((2R)-2-(3,5-di-t-butyl-4-hydroxyphenyl)thiopropanoyl)-5-ethenylpyrrolidin-2-one (33a) as a white crystalline material: mp 105°-106° C.; 1H NMR (CDCl3) δ1.37-1.42 (m, 21 H), 1.79-1.86 (m, 1 H), 1.97-2.05 (m, 1 H), 2.32-2.41 (m, 1 H), 2.57-2.67 (m, 1 H), 4.71-4.75 (t, J=6.8 Hz, 1 H), 5.03-5.17 (m, 3 H), 5.33 (s, --OH, 1 H), 5.78-5.87 (m, 1 H), 7.23 (s, 2 H); 13C NMR (CDCl3) δ174.7, 172.6, 154.7, 136.3, 135.7, 132.7, 120.9, 115.3, 58.8, 44.1, 34.3, 31.9, 30.2, 23.9, 16.4; IR (KBr) 3581 (s), 2964 (s), 1748 (vs), 1684 (vs), 1426 (s), 1345 (s), 1227 (vs), 1198 (s), 917 (w), 885 (w) cm-1.

Workup

  1. customThe cooling bath was removed
  2. customthe phases were separated
  3. extractionThe aqueous phase was extracted with t-butyl methyl ether (2×100 mL)
  4. washThe combined organic phases were washed with a saturated aqueous sodium bicarbonate solution (1×250 mL)
  5. dry with materialdried (MgSO4)
  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×24 cm length)

Sources & evidence

ORD record
ord-ce1b7e92107d4f17822db55323618241
Source dataset
uspto-grants-1993_05
Patent number
US05208345

Reaction notes

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