Trifluoroacetic acid → HCID 86593029, compound

HRID 1815555Notes

Reaction equation

HRID 1815555 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([O:13][C:14]2[CH:19]=[CH:18][C:17]([CH2:20][C@H:21]([NH:42][C:43]([O:45][C:46]([CH3:49])(C)[CH3:47])=[O:44])[C@H:22]([OH:41])[CH2:23][N:24]([CH2:37][CH:38]([CH3:40])[CH3:39])[S:25]([C:28]3[CH:33]=[CH:32][C:31]([N+:34]([O-:36])=[O:35])=[CH:30][CH:29]=3)(=[O:27])=[O:26])=[CH:16][CH:15]=2)(=[O:12])=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2].FC(F)(F)[C:52]([OH:54])=[O:53].[CH2:57](N(C(C)C)C(C)C)[CH3:58]>ClCCl>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([O:13][C:14]2[CH:19]=[CH:18][C:17]([CH2:20][C@H:21]([NH:42][C:43]([O:45][C@H:46]3[C@H:47]4[C@H:52]([O:54][CH2:57][CH2:58]4)[O:53][CH2:49]3)=[O:44])[C@H:22]([OH:41])[CH2:23][N:24]([CH2:37][CH:38]([CH3:39])[CH3:40])[S:25]([C:28]3[CH:29]=[CH:30][C:31]([N+:34]([O-:36])=[O:35])=[CH:32][CH:33]=3)(=[O:27])=[O:26])=[CH:16][CH:15]=2)(=[O:11])=[O:12])=[CH:6][CH:5]=1)([O-:3])=[O:2]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 59997351HCID 59997351, compound

Product 1

HCID 86593029HCID 86593029, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-((2S,3R)-2-[(tert-butoxycarbonyl)amino]-3-hydroxy-4-{isobutyl[(4-nitrophenyl)sulfonyl]-amino}butyl)phenyl 4-nitrobenzenesulfonate (0.21 mg, 0.29 mmol) in 10 mL of dichloromethane was added dropwise trifluoroacetic acid (2 mL). The mixture was stirred for 1 hour at room temperature. The solvents were removed under reduced pressure; the residue was redissolved in 50 mL of dichloromethane and 20 mL of 5% aqueous sodium carbonate was added. The aqueous phase was separated and extracted with dichloromethane (2×20 mL). The combined organic phases were dried over sodium carbonate, filtered, and concentrated under reduced pressure. The residue was redissolved in 10 mL of acetonitrile. N-Ethyldiisopropylamine (80 uL, 0.05 mmol) and (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl-4-nitrophenylcarbonate (0.11 g, 0.37 mmol) were added, and the solution was stirred for 12 hours. The solvents were removed under reduced pressure. The residue was redissolved in ethyl acetate (30 mL), and the organic phase was extracted with water (20 mL) followed by 5% aqueous sodium carbonate solution (5×20 mL). The organic phase was dried with sodium carbonate, filtered, and concentrated under reduced pressure. The residue was purified on silica gel using ethyl acetate-hexanes as eluent to provide 0.12 g (55%) of the title compound. 1H-NMR (CD3OD) δ 0.84 (3H,d), 0.90 (3H,d), 1.46 (1H,m), 1.58 (1H,m), 1.99 (1H,m), 2.47 (1H,t), 2.87-2.97 (2H,m), 3.04-3.10 (2H,m), 3.18 (1H,m), 3.44-3.47 (1H,dd), 3.62-3.68 (4H,m), 3.79 (1H,m), 3.89 (1H,q), 4.91 (1H,q), 5.57 (1H,d), 6.91 (2H,d), 7.20 (2H,d), 8.02-8.05 (4H,d+d), 8.36-8.42 (4H,d+d). MS: 778 (M−).

Workup

  1. customThe solvents were removed under reduced pressure
  2. dissolutionthe residue was redissolved in 50 mL of dichloromethane
  3. addition20 mL of 5% aqueous sodium carbonate was added
  4. customThe aqueous phase was separated
  5. extractionextracted with dichloromethane (2×20 mL)
  6. dry with materialThe combined organic phases were dried over sodium carbonate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. dissolutionThe residue was redissolved in 10 mL of acetonitrile
  10. stirringthe solution was stirred for 12 hours
  11. customThe solvents were removed under reduced pressure
  12. dissolutionThe residue was redissolved in ethyl acetate (30 mL)
  13. extractionthe organic phase was extracted with water (20 mL)
  14. dry with materialThe organic phase was dried with sodium carbonate
  15. filtrationfiltered
  16. concentrationconcentrated under reduced pressure
  17. customThe residue was purified on silica gel

Sources & evidence

ORD record
ord-e38d6bff4e8c45489fbb92744ce0e203
Source dataset
uspto-grants-2005_04
Patent number
US06878728B1

Reaction notes

Loading…