Trifluoroacetic acid → Benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-aminocyclohexyl)-2-oxopyrrolidin-3-ylcarbamate

HRID 554743Notes

Reaction equation

HRID 554743 reaction equation
[C:1]([NH:4][C@H:5]1[C@@H:10]([N:11]2[CH2:15][CH2:14][C@H:13]([NH:16][C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])[C:12]2=[O:27])[CH2:9][CH2:8][C@@H:7]([NH:28]C(=O)OC(C)(C)C)[CH2:6]1)(=[O:3])[CH3:2].C(O)(C(F)(F)F)=O>ClCCl>[C:1]([NH:4][C@@H:5]1[CH2:6][C@H:7]([NH2:28])[CH2:8][CH2:9][C@@H:10]1[N:11]1[CH2:15][CH2:14][C@H:13]([NH:16][C:17](=[O:18])[O:19][CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:12]1=[O:27])(=[O:3])[CH3:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86618124tert-butyl (1R,3R,4S)-3-acetamido-4-((S)-3-(benzyloxycarbonylamino)-2-oxopyrrolidin-1-yl)cyclohexylcarbamate

Product 1

HCID 44185158Benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-aminocyclohexyl)-2-oxopyrrolidin-3-ylcarbamateYield 101.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (1R,3R,4S)-3-acetamido-4-((S)-3-(benzyloxycarbonylamino)-2-oxopyrrolidin-1-yl)cyclohexylcarbamate (100 g, 0.205 mol) in dichloromethane (400 ml) was added TFA (400 ml) at −20° C. The reaction solution was stirred at room temperature for 2 h. The solvent and most of TFA were removed under reduced pressure, and the residue was diluted with dichloromethane (2 L) and aqueous K2CO3 solution (2 L). The pH was adjusted to 10 with 1N HCl. The aqueous layer was extracted with dichloromethane (3×1 L). The combined organic layer was dried over Na2SO4, and concentrated to give benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-aminocyclohexyl)-2-oxopyrrolidin-3-ylcarbamate as an oil (81 g, 100% yield). This amine was used directly in the next step without further purification.

Workup

  1. customThe solvent and most of TFA were removed under reduced pressure
  2. additionthe residue was diluted with dichloromethane (2 L) and aqueous K2CO3 solution (2 L)
  3. extractionThe aqueous layer was extracted with dichloromethane (3×1 L)
  4. dry with materialThe combined organic layer was dried over Na2SO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-8257c00603e94160ab24f40cba79df90
Source dataset
uspto-grants-2011_11
Patent number
US08049019B2

Reaction notes

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