Water → (5S)-N-((2R)-2-(2,4-di-t-butylphenyloxy)propanoyl)-5-ethenylpyrrolidin-2-one

HRID 248197Notes

Reaction equation

HRID 248197 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:20]=[C:19]([C:21]([CH3:24])([CH3:23])[CH3:22])[CH:18]=[CH:17][C:16]=1[O:25][C@H:26]([CH3:30])[C:27](Cl)=[O:28])([CH3:14])([CH3:13])[CH3:12].O>C1(C)C=CC=CC=1>[C:11]([C:15]1[CH:20]=[C:19]([C:21]([CH3:23])([CH3:22])[CH3:24])[CH:18]=[CH:17][C:16]=1[O:25][C@H:26]([CH3:30])[C:27]([N:9]1[C@H:5]([CH:3]=[CH2:4])[CH2:6][CH2:7][C:8]1=[O:10])=[O:28])([CH3:12])([CH3:13])[CH3:14]

Participants

6

Reactant 4

HCID 962WaterHCID 241505-Ethenyl-2-pyrrolidinoneHCID 24758Sodium hydrideHCID 53944384(2R)-2-(2,4-Di-t-butylphenyloxy)propanoyl chloride

Product 1

HCID 57295025(5S)-N-((2R)-2-(2,4-di-t-butylphenyloxy)propanoyl)-5-ethenylpyrrolidin-2-oneYield 48.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Conditions

Temperature
25 °C

Procedure

To 60% sodium hydride (74 mg, 2.2 mmol) in toluene (10 mL) at 0° C. was added dropwise a solution of 5-vinylpyrrolidin-2-one (222 mg, 2.0 mmol) in toluene (5 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-(2,4-di-t-butylphenyloxy)propanoyl chloride (16, 716 mg, 2.2 mmol) in toluene (5 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, 4:1). Water (30 mL) was added to the reaction mixture and the phases were separated. The aqueous phase was extracted with methylene chloride (1×25 mL). The combined organic phases were washed with a saturated aqeous sodium bicarbonate solution (1×50 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: 4.5 cm diameter×15 cm length) using hexane and ethyl acetate (19:1) afforded 360 mg (45%) of (5S)-N-((2R)-2-(2,4-di-t-butylphenyloxy)propanoyl)-5 -ethenylpyrrolidin-2-one (19a) as a thick oil: 1H NMR (CDCl3) δ1.28 (s, 9 H), 1.42 (s, 9 H), 1.77-1.80 (d, 3 H), 1.95-2.10 (m, 1 H), 2.23-2.33 (m, 1 H), 2.52-2.82 (m, 2 H), 4.91-4.97 (q, 1 H), 5.10-5.19 (m, 2 H), 5.80-5.90 (m, 1 H), 5.97-6.03 (m, 1 H), 6.49-6.53 (d, 1 H), 7.12-7.16 (d, 1 H), 7.35 (s, 1 H); 13C NMR (CDCl3) δ175.4, 172.9, 157.3, 153.4, 143.1, 137.2, 135.6, 124.3, 123.2, 115.8, 71.6, 57.9, 35.2, 34.2, 31.9, 31.4, 29.9, 24.3, 18.2; IR (neat) 2965 (vs), 1741 (vs), 1715 (vs), 1590 (s), 1230 (vs), 710 (w) cm-1.

Workup

  1. customThe cooling bath was removed
  2. customthe phases were separated
  3. extractionThe aqueous phase was extracted with methylene chloride (1×25 mL)
  4. washThe combined organic phases were washed with a saturated aqeous sodium bicarbonate solution (1×50 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: 4.5 cm diameter×15 cm length)

Sources & evidence

ORD record
ord-dba8381d7f0f42e4988ded4c466357b7
Source dataset
uspto-grants-1993_05
Patent number
US05208345

Reaction notes

Loading…