Trifluoroacetic acid → (3R,4S)-4-amino-1-(cyclopentyloxy)-5-phenyl-1-(6-quinoxalinylsulfonyl)-3-pentanol

HRID 29186Notes

Reaction equation

HRID 29186 reaction equation
[CH2:1]([C@H:8]([NH:32]C(=O)OC(C)(C)C)[C@H:9]([OH:31])[CH2:10][CH:11]([O:25][CH:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1)[S:12]([C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[N:21]=[CH:20][CH:19]=[N:18]2)(=[O:14])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O>>[NH2:32][C@@H:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C@H:9]([OH:31])[CH2:10][CH:11]([O:25][CH:26]1[CH2:27][CH2:28][CH2:29][CH2:30]1)[S:12]([C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[N:21]=[CH:20][CH:19]=[N:18]2)(=[O:13])=[O:14]

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59090730tert-butyl N-[(1S,2R)-1-benzyl-4-(cyclopentyloxy)-2-hydroxy-4-(6-quinoxalinylsulfonyl)butyl]carbamate

Product 1

HCID 57187815(3R,4S)-4-amino-1-(cyclopentyloxy)-5-phenyl-1-(6-quinoxalinylsulfonyl)-3-pentanolYield 82.4%

Procedure

A mixture of tert-butyl N-[(1S,2R)-1-benzyl-4-(cyclopentyloxy)-2-hydroxy-4-(6-quinoxalinylsulfonyl)butyl]carbamate (563 mg, 1.01 mmol) and trifluoroacetic acid (5 mL) was stirred under an Argon atmosphere for 0.5 hrs. The acid was removed in vacuo and the residue was partitioned between dichloromethane and 1N sodium hydroxide. The organic layer was separated and the aqueous layer was extracted again with dichloromethane. The combined organic layers were dried over anhydrous sodium sulfate, filtered and evaporated in vacuo. The crude product was purified on flash grade silica gel eluting with dichloromethane:methanol (98:2). Fractions containing the product were combined and evaporated in vacuo and dried under high vacuum to provide (3R,4S)-4-amino-1-(cyclopentyloxy)-5-phenyl-1-(6-quinoxalinylsulfonyl)-3-pentanol as a foam (379 mg, 82%). H1-NMR (chloroform-D3): 1.66 (m, 11H), 2.51 (m, 1H), 2.86 (m, 1H), 3.07 (m, 1H), 3.23 (m, 1H), 3.32 (m, 1H), 3.84 (m, 1H), 4.90 (m, 1H), 7.20 (m, 5H), 8.16 (m, 1H), 8.28 (d, 1H), 8.70 (m, 1H), 8.99 (m, 2H). MS (ESI): 457 (M+H).

Workup

  1. customThe acid was removed in vacuo
  2. customthe residue was partitioned between dichloromethane and 1N sodium hydroxide
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted again with dichloromethane
  5. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe crude product was purified on flash grade silica gel eluting with dichloromethane:methanol (98:2)
  9. additionFractions containing the product
  10. customevaporated in vacuo
  11. customdried under high vacuum

Sources & evidence

ORD record
ord-6e4c77e6b9c6465a8c183cfd5f26b703
Source dataset
uspto-grants-2008_09
Patent number
US07419967B2

Reaction notes

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