Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Methyl Benzoate | HCID 7150 | — |
| Reactant | Sodium hydride | HCID 24758 | — |
| Reactant | HCID 53311905 | HCID 53311905 | — |
| Solvent | Toluene | HCID 1140 | — |
| Solvent | Ammonium Chloride | HCID 25517 | — |
| Product | HCID 131733077 | HCID 131733077 | — |
Reaction Steps
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).
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
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| Patent number | US09067883B2 |
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| Source dataset | uspto-grants-2015_06 |
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| ORD ID | ord-8a9837561bef48c2bb06b33555778878 |
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| Source note | uspto-grants-2015_06 |
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