Methyl Benzoate → HCID 131733077, compound

HRID 924316Notes

Reaction equation

HRID 924316 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-01ced6055c28409790004cacb190a6b3
Source dataset
uspto-grants-2016_03
Patent number
US09278908B2

Reaction notes

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