Diisopropylethylamine → (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-[([3-(benzyloxy)phenyl]sulfonyl}(cyclohexyloxy)amino]-2-hydroxypropylcarbamate

HRID 29207

Reaction equation

HRID 29207 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([S:15](Cl)(=[O:17])=[O:16])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:19]([C@H:26]([NH:38][C:39](=[O:49])[O:40][C@@H:41]1[C@H:48]2[C@H:44]([O:45][CH2:46][CH2:47]2)[O:43][CH2:42]1)[C@H:27]([OH:37])[CH2:28][NH:29][O:30][CH:31]1[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(N(C(C)C)CC)(C)C>O1CCCC1.CN(C1C=CC=CN=1)C>[CH2:19]([C@H:26]([NH:38][C:39](=[O:49])[O:40][C@@H:41]1[C@H:48]2[C@H:44]([O:45][CH2:46][CH2:47]2)[O:43][CH2:42]1)[C@H:27]([OH:37])[CH2:28][N:29]([S:15]([C:11]1[CH:12]=[CH:13][CH:14]=[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH:10]=1)(=[O:17])=[O:16])[O:30][CH:31]1[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 157296493-(Benzyloxy)benzene-1-sulfonyl chloride2×HCID 59090777(3r,3As,6ar)hexahydrofuro[2,3-b]furan-3-yl(1s,2r)-1-benzyl-3-[(cyclohexyloxy)amino]-2-hydroxypropylcarbamate

Product 1

HCID 59090802(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-[([3-(benzyloxy)phenyl]sulfonyl}(cyclohexyloxy)amino]-2-hydroxypropylcarbamateYield 89.4%

Reagents, catalysts & solvents 2

HCID 218852-DimethylaminopyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3-benzyloxybenzenesulfonyl chloride (65 mg; 0.230 mmol), (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-[(cyclohexyloxy)amino]-2-hydroxypropylcarbamate (100 mg, 0.230 mmol) and diisoproylethylamine (0.042 mL, 0.242 mmol) in anhydrous tetrahydrofuran (3 mL) was stirred at ambient temperature under an Argon atmosphere for 16 hours. A catalytic quantity of dimethylaminopyridine (˜1 mg) was added and the reaction was heated at reflux for approximately one hour. An additional quantity of 3-benzyloxybenzenesulfonyl chloride (13 mg, 0.046 mmol) was added and the reaction was heated at reflux for approximately 1 hour. After cooling to ambient temperature, the reaction mixture was partitioned between ethyl acetate and aqueous hydrochloric acid. The phases were separated and the organic layer was then washed with brine, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The residue was dried under high vacuum to provide (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-[{[3-(benzyloxy)phenyl]sulfonyl}(cyclohexyloxy)amino]-2-hydroxypropylcarbamate (140 mg, 89%). H1-NMR (chloroform-D3): 1.22 (m, 6H), 1.62 (m, 5H), 2.05 (m, 2H), 2.90 (m, 4H), 3.11 (b, 1H), 3.66 (m, 2H), 3.87 (m, 4H), 4.18 (m, 1H), 4.77 (m, 1H), 4.95 (m, 1H), 5.10 (m, 2H), 5.60 (d, 1H), 7.29 (m, 14H). MS(ESI): 703(M+Na).

Workup

  1. temperaturethe reaction was heated
  2. temperatureat reflux for approximately one hour
  3. temperaturethe reaction was heated
  4. temperatureat reflux for approximately 1 hour
  5. temperatureAfter cooling to ambient temperature
  6. customthe reaction mixture was partitioned between ethyl acetate and aqueous hydrochloric acid
  7. customThe phases were separated
  8. washthe organic layer was then washed with brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. customevaporated in vacuo
  12. customThe residue was dried under high vacuum

Sources & evidence

ORD record
ord-7b2b68740f5a44999103e09e6f3a6e4d
Source dataset
uspto-grants-2008_09
Patent number
US07419967B2

Linked notes

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