Diisopropylethylamine → (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-3-[(1,3-benzodioxol-5-ylsulfonyl)(1-ethylpropoxy)amino]-1-benzyl-2-hydroxypropylcarbamate

HRID 29212

Reaction equation

HRID 29212 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.[O:31]1[C:35]2[CH:36]=[CH:37][C:38]([S:40](Cl)(=[O:42])=[O:41])=[CH:39][C:34]=2[O:33][CH2:32]1.C(N(C(C)C)CC)(C)C>O1CCCC1.CN(C1C=CC=CN=1)C>[O:31]1[C:35]2[CH:36]=[CH:37][C:38]([S:40]([N:11]([O:12][CH:13]([CH2:14][CH3:15])[CH2:16][CH3:17])[CH2:10][C@@H:9]([OH:18])[C@@H:8]([NH:19][C:20](=[O:30])[O:21][C@@H:22]3[C@H:29]4[C@H:25]([O:26][CH2:27][CH2:28]4)[O:24][CH2:23]3)[CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)(=[O:41])=[O:42])=[CH:39][C:34]=2[O:33][CH2:32]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 49134011,3-Benzodioxole-5-sulfonyl chlorideHCID 59090756(3R,3aS, 6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-[(l-ethylpropoxy)amino]-2-hydroxypropylcarbamate

Product 1

HCID 59090779(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-3-[(1,3-benzodioxol-5-ylsulfonyl)(1-ethylpropoxy)amino]-1-benzyl-2-hydroxypropylcarbamateYield 80%

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 (0.100 g, 0.237 mmol), 1,3-benzodioxole-5-sulfonyl chloride (52 mg, 0.237 mmol), diisoproylethylamine (0.042 mL, 0.237 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). The organic phase was separated and dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The residue was purified on a preparative TLC plate (20×20 cm, 500 uM) eluting with 97:3 dichloromethane:methanol. The product band was removed, eluted with 4:1 methylene chloride:methanol, filtered, and evaporated in vacuo. The residue was triturated with water, filtered and dried under high vacuum to provide (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-3-[(1,3-benzodioxol-5-ylsulfonyl)(1-ethylpropoxy)amino]-1-benzyl-2-hydroxypropylcarbamate (114 mg, 80%) as a white solid. H1-NMR (chloroform-D3): 0.89 (m, 6H), 1.57 (m, 7H), 2.95 (m, 5H), 3.69 (m, 2H), 3.89 (m, 4H), 4.15 (m, 1H), 4.82 (d, 1H), 5.01 (m, 1H), 5.64 (d, 1H), 6.10 (s, 2H), 6.90 (d, 1H), 7.23 (m, 6H), 7.39 (m, 1H). MS(ESI): 629(M+Na).

Workup

  1. customThe reaction was evaporated in vacuo
  2. customthe residue was partitioned between dichloromethane and aqueous hydrochloric acid (1N)
  3. customThe organic phase was separated
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was purified on a preparative TLC plate (20×20 cm, 500 uM)
  8. washeluting with 97:3 dichloromethane
  9. customThe product band was removed
  10. washeluted with 4:1 methylene chloride
  11. filtrationmethanol, filtered
  12. customevaporated in vacuo
  13. customThe residue was triturated with water
  14. filtrationfiltered
  15. customdried under high vacuum

Sources & evidence

ORD record
ord-6b5f2832e9894f7d9fc3c57353939cd3
Source dataset
uspto-grants-2008_09
Patent number
US07419967B2

Linked notes

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