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

HRID 1166515Notes

Reaction equation

HRID 1166515 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:35]=[C:36]([S:40](Cl)(=[O:42])=[O:41])[CH:37]=[CH:38][CH:39]=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:36]1[CH:37]=[CH:38][CH:39]=[C:34]([N+:31]([O-:33])=[O:32])[CH:35]=1)(=[O:41])=[O:42])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 84763-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 59787897(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-{(1-ethylpropoxy)[(3-nitrophenyl)sulfonyl]amino}-2-hydroxypropylcarbamateYield 86%

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), 3-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 hydrochloric acid (1N). After separating the phases, 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)[(3-nitrophenyl)sulfonyl]amino}-2-hydroxypropylcarbamate (246 mg, 86%). H1-NMR (chloroform-D3): 0.98 (m, 6H), 1.68 (m, 7H), 2.99 (m, 5H), 3.73 (m, 2H), 3.96 (m, 4H), 4.27 (m, 1H), 4.86 (d, 1H), 5.07 (m, 1H), 5.69 (d, 1H), 7.27 (m, 5H), 7.84 (m, 1H), 8.16 (d, 1H), 8.57 (d, 1H), 8.76 (s, 1H). MS (ESI): 630(M+Na).

Workup

  1. customThe reaction was evaporated in vacuo
  2. customthe residue was partitioned between dichloromethane and aqueous hydrochloric acid (1N)
  3. customAfter separating the phases
  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-cf06c2cc50174aab9e6c1a8ca3c5fb53
Source dataset
uspto-grants-2003_09
Patent number
US06613743B2

Reaction notes

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