Methyl Benzoate → HCID 131733077, compound

HRID 2179505Notes

Reaction equation

HRID 2179505 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]2N(CC3C=CC(OC)=CC=3)[C:11](=[O:22])[CH2:10][CH2:9]2)=[CH:3][CH:2]=1.CN1[C:35](=O)[N:34]([CH3:37])[CH2:33][CH2:32][CH2:31]1.CO[C:40](=[O:47])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.[H-].[Na+].[Cl-].[NH4+:51]>CN(C)C=O.C(OCC)(=O)C>[C:40]([C@H:10]1[CH2:9][CH:8]([CH2:7][C:4]2[CH:3]=[CH:2][C:1]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)=[CH:6][CH:5]=2)[N:51]([CH2:35][N:34]2[CH2:33][CH2:32][CH2:31][CH2:37]2)[C:11]1=[O:22])(=[O:47])[C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1

Participants

8

Reactant 5

HCID 7150Methyl BenzoateHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 53311905HCID 53311905, compound

Product 1

HCID 131733077HCID 131733077, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

Under N2, the mixture of (S)-5-biphenyl-4-ylmethyl-1-pyrrolidin-1-ylmethylpyrrolidin-2-one (3a, R1=pyrrolidinylmethyl) (1.34 g, 4 mmol), DMPU (0.56 g, 4.4 mmol) and benzoic acid methyl ester (0.6 g, 4.4 mmol) in 4 mL dimethylformamide is stirring at 20° C., sodium hydride (55% in mineral oil, 0.23 g, 5.2 mmol) is added, and stirred for 3 hours at 110° C. the reaction mixture is diluted with 5 mL saturated aqueous ammonium chloride solution and 10 mL ethyl acetate, 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. Spectroscopic data as Example 6, Method 1.

Workup

  1. stirringstirred for 3 hours at 110° C. the reaction mixture
  2. stirringstirred for 15 min
  3. stirringstop stirring
  4. customremove the lower aqueous layer
  5. concentrationthe organic phase is concentrated to dryness
  6. customthe residue was purified by column chromatography (ethyl acetate/heptane=1/1)

Sources & evidence

ORD record
ord-1e223eca1b4f4661979d8d9b806c124c
Source dataset
uspto-grants-2015_06
Patent number
US09067883B2

Reaction notes

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