Toluene → HCID 86673650, compound

HRID 924323Notes

Reaction equation

HRID 924323 reaction equation
[C:1]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]2[N:12]([CH2:13][C:14]3[CH:19]=[CH:18][C:17](OC)=[CH:16][CH:15]=3)[C:11](=[O:22])[CH2:10][CH2:9]2)=[CH:3][CH:2]=1.[H-].[Na+].[C:31](Cl)(=[O:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.[C:40]1(C)C=CC=CC=1>[Cl-].[NH4+]>[C:31]([C@@H:10]1[CH2:9][CH:8]([CH2:7][C:4]2[CH:5]=[CH:6][C:1]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)=[CH:2][CH:3]=2)[N:12](/[CH:13]=[CH:14]/[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:40]=2)[C:11]1=[O:22])(=[O:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 7412Benzoyl chlorideHCID 24758Sodium hydrideHCID 53311905HCID 53311905, compound

Product 1

HCID 86673650HCID 86673650, compound

Reagents, catalysts & solvents 1

HCID 25517Ammonium ChlorideSolvent

Procedure

Under N2, 1-benzoyl-(S)-5-biphenyl-4-ylmethyl-pyrrolidin-2-one (3a, R1=benzoyl) (1.34 g, 4 mmol) is dissolved in 4 mL toluene, and heated to reflux, sodium hydride (55% in mineral oil, 0.23 g, 5.2 mmol) is added, and stirred for 2 hours at reflux, then benzoyl chloride (0.62 g, 4.4 mmol) is added to the reaction mixture, the resulting mixture is then stirred for 2 hours at reflux. the reaction mixture is diluted with 5 mL saturated aqueous ammonium chloride solution and stirred for 15 min, stop stirring, and remove the lower aqueous layer. The organic phase is concentrated to dryness, the residue is purified by column chromatography (ethyl acetate/heptane=1/2) to yield (R/S)-1,3-Dibenzoyl-(S)-5-biphenyl-4-ylmethyl-pyrrolidin-2-one (4a, R1=benzoyl, R4=phenyl), the ratio of (3S,5S) to (3R,5S) is 30:70 as determined by HPLC. 1HNMR (400 MHz, CDCl3): 2.09 (m, 1H, 3-CHH), 2.34 (m, 1H, 3-CHH), 2.71 (d, 1H, 5-CHH), 2.96 (d, 1H, 5-CHH), 3.73 (m, 1H, 2-CH), 4.38 (m, 1H, 4-CH), 7.20˜8.10 (19H, m, aromatic).

Workup

  1. temperatureheated
  2. temperatureto reflux
  3. temperatureat reflux
  4. stirringthe resulting mixture is then stirred for 2 hours
  5. temperatureat reflux
  6. stirringstirred for 15 min
  7. stirringstop stirring
  8. customremove the lower aqueous layer
  9. concentrationThe organic phase is concentrated to dryness
  10. customthe residue is purified by column chromatography (ethyl acetate/heptane=1/2)

Sources & evidence

ORD record
ord-85677fdf440346d49d34d2259e40658b
Source dataset
uspto-grants-2016_03
Patent number
US09278908B2

Reaction notes

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