Methyl Benzoate → HCID 131733077, compound

HRID 924314Notes

Reaction equation

HRID 924314 reaction equation
[C:1]1(C2C=CC=CC=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]2[N:12]([CH2:13]C3C=CC(OC)=CC=3)[C:11](=[O:22])[CH2:10][CH2:9]2)=[CH:3][CH:2]=1.CO[C:31](=[O:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.[H-].[Na+]>C1(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:4]3[CH:3]=[CH:2][CH:1]=[CH:6][CH:5]=3)=[CH:2][CH:3]=2)[N:12]([CH2:13][N:12]2[CH2:8][CH2:9][CH2:10][CH2:11]2)[C:11]1=[O:22])(=[O:38])[C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1

Participants

6

Reactant 3

HCID 7150Methyl BenzoateHCID 24758Sodium hydrideHCID 53311905HCID 53311905, compound

Product 1

HCID 131733077HCID 131733077, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 25517Ammonium ChlorideSolvent

Procedure

Under N2, the mixture of (S)-5-biphenyl-4-ylmethyl-1-pyrrolidin-1-ylmethylpyrrolidin-2-one (3a, R1=pyrrolidinylmethyl) (6.68 g, 20 mmol) and benzoic acid methyl ester (3.0 g, 22 mmol) in 20 mL toluene is heated to reflux, sodium hydride (55% in mineral oil, 1.14 g, 26 mmol) is added, and stirred overnight at reflux. The reaction mixture is diluted with 20 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 was purified by column chromatography (ethyl acetate/heptane=1/1) to give (R/S)-3-Benzoyl-(R)-5-biphenyl-4-ylmethyl-1-pyrrolidin-1-ylmethyl-pyrrolidin-2-one (4a, R1=pyrrolidinylmethyl, R4=phenyl), the ratio of (3S,5R) and (3R,5R) is 60:40 as determined by HPLC. 1HNMR (400 MHz, CDCl3): 1.68 (m, 4H, 2×CH2CH2), 1.98 (m, 1H, 3-CHH), 2.23 (m, 1H, 3-CHH), 2.51 (m, 4H, 2×NCH2), 2.65 (dd, 1H, N—CHH), 3.15 (dd, 1H, N—CHH), 2.67 (d, 1H, 5-CHH), 2.92 (d, 1H, 5-CHH), 3.73 (m, 1H, 2-CH), 3.78 (m, 1H, 4-CH), 7.20-8.00 (14H, m, aromatic).

Workup

  1. temperatureis heated
  2. temperatureto reflux
  3. temperatureat reflux
  4. stirringstirred for 15 min
  5. stirringstop stirring
  6. customremove the lower aqueous layer
  7. concentrationthe organic phase is concentrated to dryness
  8. customthe residue was purified by column chromatography (ethyl acetate/heptane=1/1)

Sources & evidence

ORD record
ord-00307f165d4f49f7b2b70394e18d3f07
Source dataset
uspto-grants-2016_03
Patent number
US09278908B2

Reaction notes

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