Dichloromethane → HCID 86596888, compound

HRID 1171564Notes

Reaction equation

HRID 1171564 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]([C:35]([CH3:38])([CH3:37])[CH3:36])(=[O:34])=[O:33])[C:13]1=[O:39])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.F[C:41](F)(F)[C:42](O)=O.[CH2:47](Cl)Cl>>[C:35]([S:32]([CH2:31][C@@H:18]1[CH2:19][C@H:20]([N:23]([CH:41]([CH3:42])[CH3:47])[CH3:24])[CH2:21][CH2:22][C@@H:17]1[N:14]1[CH2:15][CH2:16][C@H:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:13]1=[O:39])(=[O:34])=[O:33])([CH3:36])([CH3:37])[CH3:38]

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 86596886HCID 86596886, compound

Product 1

HCID 86596888HCID 86596888, compound

Procedure

tert-Butyl (1R,3R,4S)-4-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-3-(tert-butylsulfonylmethyl)cyclohexylcarbamate (880 mg) was dissolved in CH2Cl2 (5 mL) at 0° C. prior to the addition of trifluoroacetic acid (10 mL). After 1 h at rt, the reaction was concentrated in vacuo. The resultant residue was dissolved in EtOAc and was washed with sat. Na2CO3 solution. The organic phase was dried (MgSO4), filtered, and concentrated. This residue was dissolved in dichloroethane (6 ml) and acetone (6 mL) prior to the addition of NaBH(OAc)3 (637.6 mg). After 2 h, formaldehyde (6.0 mL of a 37% aq. solution) was added along with NaBH(OAc)3 (310 mg). The mixture was stirred for 1 h, quenched with sat. Na2CO3, and extracted with EtOAc (2×). The organic extracts were combined, dried (MgSO4), filtered, and concentrated to afford benzyl (S)-1-((1S,2R,4R)-2-(tert-butylsulfonylmethyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate (1.0 g). MS found: (M+H)+=522.5.

Workup

  1. concentrationthe reaction was concentrated in vacuo
  2. dissolutionThe resultant residue was dissolved in EtOAc
  3. washwas washed with sat. Na2CO3 solution
  4. dry with materialThe organic phase was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThis residue was dissolved in dichloroethane (6 ml)
  8. additionacetone (6 mL) prior to the addition of NaBH(OAc)3 (637.6 mg)
  9. waitAfter 2 h
  10. additionformaldehyde (6.0 mL of a 37% aq. solution) was added along with NaBH(OAc)3 (310 mg)
  11. customquenched with sat. Na2CO3
  12. extractionextracted with EtOAc (2×)
  13. dry with materialdried (MgSO4)
  14. filtrationfiltered
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-dd8a0a562f1548b6a28ea4bc7a4cfa58
Source dataset
uspto-grants-2010_11
Patent number
US07829571B2

Reaction notes

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