3,5-Di-tert-butyl-1,2-benzoquinone → benzyl (S)-1-((1S,2R)-2-acetamido-4-oxocyclohexyl)-2-oxopyrrolidin-3-ylcarbamate

HRID 2246601Notes

Reaction equation

HRID 2246601 reaction equation
[C:1]([NH:4][C@@H:5]1[CH2:10][C@H:9](N)[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].C(C1C(=O)C(=[O:43])C=C(C(C)(C)C)C=1)(C)(C)C>CO.CCOC(C)=O>[C:1]([NH:4][C@@H:5]1[CH2:10][C:9](=[O:43])[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]

Participants

5

Reactant 2

HCID 769153,5-Di-tert-butyl-1,2-benzoquinoneHCID 44185158Benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-aminocyclohexyl)-2-oxopyrrolidin-3-ylcarbamate

Product 1

HCID 25031311benzyl (S)-1-((1S,2R)-2-acetamido-4-oxocyclohexyl)-2-oxopyrrolidin-3-ylcarbamate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-aminocyclohexyl)-2-oxopyrrolidin-3-ylcarbamate (13.3 g, 34 mmol) and 3,5-di-tert-butylcyclohexa-3,5-diene-1,2-dione (7.54 g, 34 mmol) in methanol (160 ml) was stirred at room temperature for 2 h. The solution was concentrated and diluted with acetone (132 ml) and water (33 ml), followed by addition of Dowex-50WX8-200 (33 g). The reaction was stirred at room temperature for 2 h. Dowex-50WX8-200 was removed by filtration and washed with dichloromethane (300 ml). The filtrate was concentrated under vacuum to remove most of acetone. The residue was diluted with dichloromethane (200 ml) and washed with aqueous NaHCO3 solution (200 ml) and brine (200 ml). The combined aqueous layers were extracted with dichloromethane (2×100 ml). The combined organic extracts were dried over Na2SO4 and concentrated. The product benzyl (S)-1-((1S,2R)-2-acetamido-4-oxocyclohexyl)-2-oxopyrrolidin-3-ylcarbamate was obtained as a solid (12 g, 90% yield) by crystallization in EtOAc (100 ml) and Hexane (200 ml). 1H-NMR (500 MHz, DMSO-d6) δ ppm 7.99 (d, J=9.35 Hz, 1H), 7.44 (d, J=8.80 Hz, 1H), 7.28-7.39 (m, 5H), 5.03 (s, 2H), 4.50 (s, 1H), 4.31 (d, J=12.10 Hz, 1H), 4.18 (q, J=8.98 Hz, 1H), 3.27 (m, 2H), 2.82 (dd, J=15.12, 5.22 Hz, 1H), 2.52-2.65 (m, 1H), 2.40 (dd, J=12.92, 4.67 Hz, 1H), 2.15-2.31 (m, 2H), 2.09 (d, J=15.40 Hz, 1H), 1.90 (m, 1H), 1.81 (s, 3H), 1.68 (m, 1H). m/z: 388.46 [M+H].

Workup

  1. concentrationThe solution was concentrated
  2. additiondiluted with acetone (132 ml) and water (33 ml)
  3. additionfollowed by addition of Dowex-50WX8-200 (33 g)
  4. customDowex-50WX8-200 was removed by filtration
  5. washwashed with dichloromethane (300 ml)
  6. concentrationThe filtrate was concentrated under vacuum
  7. customto remove most of acetone
  8. additionThe residue was diluted with dichloromethane (200 ml)
  9. washwashed with aqueous NaHCO3 solution (200 ml) and brine (200 ml)
  10. extractionThe combined aqueous layers were extracted with dichloromethane (2×100 ml)
  11. dry with materialThe combined organic extracts were dried over Na2SO4
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-dc97d7b6647e4acb830ea512453cecf3
Source dataset
uspto-grants-2010_03
Patent number
US07687508B2

Reaction notes

Loading…