Acetic Acid → HCID 53311905, compound

HRID 924313Notes

Reaction equation

HRID 924313 reaction equation
[H-].[Na+].[C:3]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:8]=[CH:7][C:6]([CH2:9][C@H:10]2[NH:14][C:13](=[O:15])[CH2:12][CH2:11]2)=[CH:5][CH:4]=1.[CH3:22][O:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28]Cl)=[CH:26][CH:25]=1.CC(O)=O>CN(C)C=O>[C:3]1([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:4]=[CH:5][C:6]([CH2:9][C@H:10]2[N:14]([CH2:28][C:27]3[CH:30]=[CH:31][C:24]([O:23][CH3:22])=[CH:25][CH:26]=3)[C:13](=[O:15])[CH2:12][CH2:11]2)=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 24758Sodium hydrideHCID 699934-Methyloxybenzyl chlorideHCID 58160438(S)-5-[(Biphenyl-4-yl)methyl]pyrrolidin-2-one

Product 1

HCID 53311905HCID 53311905, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

Under N2, sodium hydride (55%, 6.9 g, 158 mmol) is added to the mixture of (S)-5-biphenyl-4-ylmethylpyrrolidin-2-one (3a, R1=H) (36 g, 143 mmol) in 400 mL dry dimethylformamide at r.t., then 4-methoxybenzyl chloride (24.7 g, 158 mmol) is added. The reaction mixture is heated to 55° C. and stirred for 3 h. Cooled to r.t., 5 mL AcOH is added, and stirred for another 15 min, then dimethylformamide is removed, the residue is redissolved in 400 mL ethyl acetate, washed with water, dried with sodium sulfate. The solvent is removed, the residue is redissolved in 100 mL tert-butylmethylether, cooled to 0° C. and stirred for 5 h, filtered, and dried to afford (S)-5-biphenyl-4-ylmethyl-1-(4-methoxy-benzyl)-pyrrolidin-2-one (3a, R1=p-methoxybenzyl). 1HNMR (400 MHz, CDCl3): 1.78 (m, 1H, 3-CHH), 1.90 (m, 1H, 3-CHH), 2.28 (m, 2H, 2-CH2), 2.59 (dd, 1H, 5-CHH), 3.05 (dd, 1H, 5-CHH), 3.80 (s, 3H, OCH3), 3.98 (d, 1H, CHH), 5.05 (d, 1H, CHH), 6.80˜7.40 (13H, m, aromatic).

Workup

  1. temperatureCooled to r.t.
  2. stirringstirred for another 15 min
  3. customdimethylformamide is removed
  4. dissolutionthe residue is redissolved in 400 mL ethyl acetate
  5. washwashed with water
  6. dry with materialdried with sodium sulfate
  7. customThe solvent is removed
  8. dissolutionthe residue is redissolved in 100 mL tert-butylmethylether
  9. temperaturecooled to 0° C.
  10. stirringstirred for 5 h
  11. filtrationfiltered
  12. customdried

Sources & evidence

ORD record
ord-60f6fc2861e24bdc909d09aad1a3240e
Source dataset
uspto-grants-2016_03
Patent number
US09278908B2

Reaction notes

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