Toluene → HCID 131733077, compound

HRID 924317Notes

Reaction equation

HRID 924317 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.C[N:30]1[C:35](=O)N(C)[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+].[C:50]1(C)[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1>[Cl-].[NH4+].C(OCC)(=O)C>[C:40]([C@H:10]1[CH2:9][CH:8]([CH2:7][C:4]2[CH:5]=[CH:6][C:1]([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)=[CH:2][CH:3]=2)[N:12]([CH2:13][N:30]2[CH2:31][CH2:32][CH2:33][CH2:35]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 1140TolueneHCID 7150Methyl BenzoateHCID 24758Sodium hydrideHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 53311905HCID 53311905, compound

Product 1

HCID 131733077HCID 131733077, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

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 Toluene 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 60° 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 60° 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-e25b03146ae443c4ba5d56321514f85b
Source dataset
uspto-grants-2016_03
Patent number
US09278908B2

Reaction notes

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