Trifluoroacetic acid → benzyl (S)-1-((1S,2R,4R)-4-(tert-butylamino)-2-(methylsulfonamido)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate

HRID 2246599Notes

Reaction equation

HRID 2246599 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]([CH3:27])([CH3:26])[CH3:25])[CH2:19][C@H:18]2[NH:28]C(=O)OCC[Si](C)(C)C)[C:13]1=[O:38])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.C(N(CC)CC)C.[CH3:53][S:54](Cl)(=[O:56])=[O:55]>ClCCl>[C:24]([NH:23][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:38])[C@H:18]([NH:28][S:54]([CH3:53])(=[O:56])=[O:55])[CH2:19]1)([CH3:27])([CH3:26])[CH3:25]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 866181402-(trimethylsilyl)ethyl (1R,2S,5R)-2-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexylcarbamate

Product 1

HCID 86618161benzyl (S)-1-((1S,2R,4R)-4-(tert-butylamino)-2-(methylsulfonamido)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamateYield 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A sample of 2-(trimethylsilyl)ethyl (1R,2S,5R)-2-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexylcarbamate and its 5S diastereomer (100 mg, 0.183 mmol; see Example 11, Step 4) was dissolved in dichloromethane (2 ml) prior to the addition of trifluoroacetic acid (2.54 ml, 32.9 mmol). After 30 min, the solution was concentrated in vacuo. The residue was dissolved in dichloromethane (3 ml) prior to the addition of triethylamine (0.100 ml, 0.720 mmol) and methanesulfonyl chloride (0.018 ml, 0.234 mmol). After 2 h, this was washed with sat NaHCO3 solution and the organic layer was dried (Na2SO4), filtered and concentrated to afford benzyl (S)-1-((1S,2R,4R)-4-(tert-butylamino)-2-(methylsulfonamido)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate as a mixture with its 4S diastereomer (66 mg, 0.137 mmol, 76% yield). LC/MS found [M+H]+=481.22.

Workup

  1. concentrationthe solution was concentrated in vacuo
  2. dissolutionThe residue was dissolved in dichloromethane (3 ml)
  3. waitAfter 2 h
  4. washthis was washed with sat NaHCO3 solution
  5. dry with materialthe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-2186736fbb664688bb2696d8775e1028
Source dataset
uspto-grants-2010_03
Patent number
US07687508B2

Reaction notes

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