Acetone → benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-(isopropylamino)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate

HRID 2246570Notes

Reaction equation

HRID 2246570 reaction equation
[C:1]([NH:4][C@@H:5]1[CH2:10][C@H:9]([NH2:11])[CH2:8][CH2:7][C@@H:6]1[N:12]1[CH2:16][CH2:15][C@H:14]([NH:17][C:18](=[O:27])[O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:13]1=[O:28])(=[O:3])[CH3:2].[CH3:29][C:30]([CH3:32])=O.C([O-])(=O)C.[Na+].C([BH3-])#N.[Na+]>CO>[C:1]([NH:4][C@@H:5]1[CH2:10][C@H:9]([NH:11][CH:30]([CH3:32])[CH3:29])[CH2:8][CH2:7][C@@H:6]1[N:12]1[CH2:16][CH2:15][C@H:14]([NH:17][C:18](=[O:27])[O:19][CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:13]1=[O:28])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 180AcetoneHCID 517045Sodium AcetateHCID 5003444Sodium cyanoborohydrideHCID 44185158Benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-aminocyclohexyl)-2-oxopyrrolidin-3-ylcarbamate

Product 1

HCID 44185159benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-(isopropylamino)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A stirring solution of benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-aminocyclohexyl)-2-oxopyrrolidin-3-ylcarbamate (˜0.135 mol) in methanol (675 mL) was charged sequentially with acetone (37.8 g, 4 eq), sodium acetate (33.2 g, 3 eq), and sodium cyanoborohydride (16.9 g, 2 eq). The mixture was stirred at room temperature for 6 h and filtered. The filtrate was dissolved in dichloromethane (1 L); this solution was washed with 1N NaOH (1 L). The solids collected in the filtration were dissolved in 1N NaOH (1 L) at 0° C. and then extracted with dichloromethane (1 L). The organic extracts were combined and extracted with aqueous HCl (200 mL 1N HCl+800 mL water). The aqueous phase was basified with sat. NaHCO3 (500 mL) and then 1N NaOH (100 mL) until pH 11. The aqueous phase was extracted with dichloromethane (2 L). The organic extracts were combined, dried (Na2SO4), filtered, and concentrated in vacuo to give benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-(isopropylamino)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate as an oil. LC/MS found [M+H]+=431.45. 1H-NMR (400 MHz, d4-MeOH): δ 7.3-7.4 (m, 5H), 5.12 (s, 2H), 4.31 (m, 1H), 4.24 (t, J=9.4 Hz, 1H), 4.11 (m, 1H), 3.61 (t, J=9.1 Hz, 1H), 3.52 (q, J=8.6 Hz, 1H), 3.04 (br. s, 1H), 2.96 (sep, J=6.3 Hz, 1H), 2.40 (m, 1H), 2.15 (m, 1H), 1.92 (s, 3H), 1.7-1.9 (m, 5H), 1.65 (m, 1H), 1.12 (app. dd, J=6.3, 1.1 Hz, 6H).

Workup

  1. filtrationfiltered
  2. dissolutionThe filtrate was dissolved in dichloromethane (1 L)
  3. washthis solution was washed with 1N NaOH (1 L)
  4. filtrationThe solids collected in the filtration
  5. dissolutionwere dissolved in 1N NaOH (1 L) at 0° C.
  6. extractionextracted with dichloromethane (1 L)
  7. extractionextracted with aqueous HCl (200 mL 1N HCl+800 mL water)
  8. extractionThe aqueous phase was extracted with dichloromethane (2 L)
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a7401bc4437f4fc780909b83a33d343d
Source dataset
uspto-grants-2010_03
Patent number
US07687508B2

Reaction notes

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