Dichloromethane → HCID 86596884, compound

HRID 1374329Notes

Reaction equation

HRID 1374329 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:16][CH2:15][N:14]([C@H:17]2[CH2:22][CH2:21][C@@H:20]([NH:23][C:24](=O)OC(C)(C)C)[CH2:19][C@H:18]2[CH2:31][S:32]([CH3:35])(=[O:34])=[O:33])[C:13]1=[O:36])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.F[C:38](F)(F)[C:39](O)=O.[CH2:44](Cl)Cl>>[CH:38]([N:23]([CH3:24])[C@@H:20]1[CH2:21][CH2:22][C@H:17]([N:14]2[CH2:15][CH2:16][C@H:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C:13]2=[O:36])[C@H:18]([CH2:31][S:32]([CH3:35])(=[O:34])=[O:33])[CH2:19]1)([CH3:39])[CH3:44]

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 86596880HCID 86596880, compound

Product 1

HCID 86596884HCID 86596884, compound

Procedure

Tert-butyl (1R,3R,4S)-4-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-3-(methylsulfonylmethyl)cyclohexylcarbamate (714 mg) was dissolved in CH2Cl2 (15 mL) prior to the addition of trifluoroacetic acid (7 mL). After 1 h at rt, the reaction was concentrated in vacuo. This residue was dissolved in MeOH (15 mL) and charged with acetone (1.0 mL) and NaOAc (558 mg). The mixture was stirred for 5 min before being charged with NaCNBH3 (461 mg). The reaction was stirred for 2 h and then charged with formaldehyde (0.5 mL of a 37% aq. solution) and NaCNBH3 (461 mg). The mixture was stirred for 1 h, quenched with sat. NaHCO3, and extracted with EtOAc (2×). The organic extracts were combined, dried (MgSO4), filtered, and concentrated to afford the benzyl (S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(methylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate (1.5 g). MS found: (M+H)+=466.4.

Workup

  1. concentrationthe reaction was concentrated in vacuo
  2. dissolutionThis residue was dissolved in MeOH (15 mL)
  3. additioncharged with acetone (1.0 mL) and NaOAc (558 mg)
  4. additionbefore being charged with NaCNBH3 (461 mg)
  5. stirringThe reaction was stirred for 2 h
  6. additioncharged with formaldehyde (0.5 mL of a 37% aq. solution) and NaCNBH3 (461 mg)
  7. stirringThe mixture was stirred for 1 h
  8. customquenched with sat. NaHCO3
  9. extractionextracted with EtOAc (2×)
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-23ac48587e974032bc6177297113d28a
Source dataset
uspto-grants-2007_01
Patent number
US07163937B2

Reaction notes

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