Toluene → HCID 86673650, compound

HRID 924322Notes

Reaction equation

HRID 924322 reaction equation
[H-].[Na+].[C:3]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:8]=[CH:7][C:6]([CH2:9][C@H:10]2[N:14]([CH2:15][C:16]3[CH:21]=[CH:20][C:19](OC)=[CH:18][CH:17]=3)[C:13](=[O:24])[CH2:12][CH2:11]2)=[CH:5][CH:4]=1.[C:31](OC)(=[O:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.[C:41]1(C)C=CC=CC=1>>[C:31]([C@@H:12]1[CH2:11][CH:10]([CH2:9][C:6]2[CH:7]=[CH:8][C:3]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)=[CH:4][CH:5]=2)[N:14](/[CH:15]=[CH:16]/[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:41]=2)[C:13]1=[O:24])(=[O:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

5

Reactant 4

HCID 1140Toluene2×HCID 7150Methyl BenzoateHCID 24758Sodium hydrideHCID 53311905HCID 53311905, compound

Product 1

HCID 86673650HCID 86673650, compound

Procedure

Sodium hydride (2.03 g, 46.4 mmol) is suspended in 40-mL of anhydrous toluene, heat to reflux under nitrogen atmosphere, add a mixture solution of (S)-5-Biphenyl-4-ylmethyl-1-((E)-but-1-enyl)-pyrrolidin-2-one (3a, R1=1-butenyl) (11.02 g, 35.67 mmol) and methyl benzoate (4.86 g, 35.67 mmol) in anhydrous toluene dropwise, the reaction mixture is refluxed for 4 h, cool to ambient temperature, quench with saturated NH4Cl aqueous solution, extracted with toluene, the combined organic extracts are washed with saturated Na2CO3 and brine, dry over anhydrous Na2SO4, concentrate under vacuum to obtain (S)-3-Benzoyl-5-biphenyl-4-ylmethyl-1-((E)-but-1-enyl)-pyrrolidin-2-one (4a, R1=1-butenyl, R4=benzyl), which is directly used in the next step. 1HNMR (400 MHz, CDCl3): 1.07 (t, 3H, CH3H), 2.12 (m, 2H, CH2H), 2.20 (m, 2H, 3-CH2), 2.95 (m, 1H, 5-CH2), 3.13 (m, 1H, 5-CH2), 3.82 (m, H, 2-CH2H), 4.14 (m, 1H, 4-CH), 5.27 (m, 1H, CH═CH), 6.85 (d, 1H, HC═CH—N), 7.14˜8.20 (14H, m, aromatic). the ratio of (3S,5S) to (3R,5S) is 60:40 as determined by HPLC.

Workup

  1. temperatureheat
  2. temperatureto reflux under nitrogen atmosphere
  3. temperaturethe reaction mixture is refluxed for 4 h
  4. customquench with saturated NH4Cl aqueous solution
  5. extractionextracted with toluene
  6. washthe combined organic extracts are washed with saturated Na2CO3 and brine
  7. dry with materialdry over anhydrous Na2SO4
  8. concentrationconcentrate under vacuum

Sources & evidence

ORD record
ord-5e30ff50eb574995a4c7a7b5361d2124
Source dataset
uspto-grants-2016_03
Patent number
US09278908B2

Reaction notes

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