反応 #57490

反応方程式

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

1,3-benzodioxole-5-sulfonyl chloride

diisoproylethylamine

→

(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

収率 80.0%

溶媒

tetrahydrofuran

反応条件

後処理

1. 1
   その他The reaction was evaporated in vacuo
2. 2
   その他the residue was partitioned between dichloromethane and aqueous hydrochloric acid (1N)
3. 3
   その他The organic phase was separated
4. 4
   乾燥dried over anhydrous magnesium sulfate
5. 5
   ろ過filtered
6. 6
   その他evaporated in vacuo
7. 7
   その他The residue was purified on a preparative TLC plate (20×20 cm, 500 uM)
8. 8
   洗浄eluting with 97:3 dichloromethane
9. 9
   その他The product band was removed
10. 10
    洗浄eluted with 4:1 methylene chloride
11. 11
    ろ過methanol, filtered
12. 12
    その他evaporated in vacuo
13. 13
    その他The residue was triturated with water
14. 14
    ろ過filtered
15. 15
    その他dried under high vacuum

実験手順

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).

出典