4-Nitrobenzenesulfonyl chloride → (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-{(1-ethylpropoxy)[(4-nitrophenyl)sulfonyl]amino}-2-hydroxypropylcarbamate

HRID 1166513Notes

Reaction equation

HRID 1166513 reaction equation
[CH2:1]([C@H:8]([NH:19][C:20](=[O:30])[O:21][C@@H:22]1[C@H:29]2[C@H:25]([O:26][CH2:27][CH2:28]2)[O:24][CH2:23]1)[C@H:9]([OH:18])[CH2:10][NH:11][O:12][CH:13]([CH2:16][CH3:17])[CH2:14][CH3:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N+:31]([C:34]1[CH:39]=[CH:38][C:37]([S:40](Cl)(=[O:42])=[O:41])=[CH:36][CH:35]=1)([O-:33])=[O:32].C(N(C(C)C)CC)(C)C>O1CCCC1.CN(C1C=CC=CN=1)C>[CH2:1]([C@H:8]([NH:19][C:20](=[O:30])[O:21][C@@H:22]1[C@H:29]2[C@H:25]([O:26][CH2:27][CH2:28]2)[O:24][CH2:23]1)[C@H:9]([OH:18])[CH2:10][N:11]([O:12][CH:13]([CH2:14][CH3:15])[CH2:16][CH3:17])[S:40]([C:37]1[CH:36]=[CH:35][C:34]([N+:31]([O-:33])=[O:32])=[CH:39][CH:38]=1)(=[O:41])=[O:42])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 74044-Nitrobenzenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 59090756(3R,3aS, 6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-[(l-ethylpropoxy)amino]-2-hydroxypropylcarbamate

Product 1

HCID 59787925(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-{(1-ethylpropoxy)[(4-nitrophenyl)sulfonyl]amino}-2-hydroxypropylcarbamateYield 88.2%

Reagents, catalysts & solvents 2

HCID 218852-DimethylaminopyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-[(1-ethylpropoxy)amino]-2-hydroxypropylcarbamate (200 mg, 0.474 mmol), 4-nitrophenylsulphonyl chloride (105 mg, 0.474 mmol), diisoproylethylamine (0.084 mL, 0.474 mmol) and dimethylaminopyridine (˜1 mg) in anhydrous tetrahydrofuran (3 mL) was stirred at ambient temperature over 16 hours under an Argon atmosphere. The reaction was evaporated in vacuo and the residue was partitioned between dichloromethane and aqueous sodium hydrogen sulfate (1N). The phases were separated and the aqueous layer was extracted with dichloromethane. The combined organic phases were dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The residue was purified on flash grade silica gel eluting with 1:1 ethyl acetate:hexane. Fractions containing the product were combined, evaporated in vacuo and dried under high vacuum to provide (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-{(1-ethylpropoxy)[(4-nitrophenyl)sulfonyl]amino}-2-hydroxypropylcarbamate (254 mg, 88%) as a foam. H1-NMR (chloroform-D3): 0.90 (m, 6H), 1.60 (m, 7H), 2.90 (m, 5H), 3.68 (m, 2H), 3.87 (m, 4H), 4.17 (m, 1H), 4.83 (d, 1H), 5.02 (m, 1H), 5.64 (d, 1H), 7.23 (m, 5H), 7.99 (d, 2H), 8.38 (d, 2H). MS(ESI): 630(M+Na).

Workup

  1. customThe reaction was evaporated in vacuo
  2. customthe residue was partitioned between dichloromethane and aqueous sodium hydrogen sulfate (1N)
  3. customThe phases were separated
  4. extractionthe aqueous layer was extracted with dichloromethane
  5. dry with materialThe combined organic phases were dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue was purified on flash grade silica gel eluting with 1:1 ethyl acetate
  9. additionFractions containing the product
  10. customevaporated in vacuo
  11. customdried under high vacuum

Sources & evidence

ORD record
ord-368aac35af5f4fd8b077b1a5ee3460cb
Source dataset
uspto-grants-2003_09
Patent number
US06613743B2

Reaction notes

Loading…