Acetone → benzyl (S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(isopropylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate

HRID 1455432Notes

Reaction equation

HRID 1455432 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][C@H:5]([N:8]2[CH2:12][CH2:11][C@H:10]([NH:13][C:14](=[O:23])[O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:9]2=[O:24])[C@H:4]([CH2:25][S:26]([CH:29]([CH3:31])[CH3:30])(=[O:28])=[O:27])[CH2:3]1.[CH3:32][C:33]([CH3:35])=O.[C:36]([BH3-])#N.[Na+].C=O>C(Cl)Cl>[CH:33]([N:1]([CH3:36])[C@@H:2]1[CH2:7][CH2:6][C@H:5]([N:8]2[CH2:12][CH2:11][C@H:10]([NH:13][C:14](=[O:23])[O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:9]2=[O:24])[C@H:4]([CH2:25][S:26]([CH:29]([CH3:31])[CH3:30])(=[O:28])=[O:27])[CH2:3]1)([CH3:35])[CH3:32]

Participants

6

Reactant 4

HCID 180AcetoneHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydride2×HCID 86596892benzyl (S)-1-((1S,2R,4R)-4-amino-2-(isopropylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate

Product 1

HCID 86596891benzyl (S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(isopropylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The entirety of benzyl benzyl (S)-1-((1S,2R,4R)-4-amino-2-(isopropylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate prepared in Step 1 (1 eq) was dissolved in CH2Cl2 (20 mL). The resultant solution was charged with acetone (10 eq) and stirred at RT for 10 min before sodium cyanoborohydride (2 eq) was added in one portion. The reaction was stirred at RT for 10 h and then charged successively with formaldehyde (10 eq. in 37 wt % aq soln) and sodium cyanoborohydride (2 eq). The reaction was stirred for another 9 h at RT and then quenched with sat. NaHCO3. The aqueous mixture was extracted with EtOAc (200 mL, then 2×75 mL). The organic extracts were combined, washed with brine (30 mL), dried (MgSO4), filtered, and concentrated in vacuo. After the resulting oil stood, some paraformaldehyde-related products solidified; these were removed by dissolving the mixture in a minimal volume of EtOAc and filtering. Subsequent concentration provided benzyl (S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(isopropylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate. MS found: (M+H)+=508.

Workup

  1. additionwas added in one portion
  2. stirringThe reaction was stirred for another 9 h at RT
  3. customquenched with sat. NaHCO3
  4. extractionThe aqueous mixture was extracted with EtOAc (200 mL
  5. washwashed with brine (30 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customthese were removed
  10. dissolutionby dissolving the mixture in a minimal volume of EtOAc
  11. filtrationfiltering
  12. concentrationSubsequent concentration

Sources & evidence

ORD record
ord-43aac01013e94b1fa5c5a03da9b7a8b1
Source dataset
uspto-grants-2009_01
Patent number
US07482335B2

Reaction notes

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