Diisopropylethylamine → (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-[{[4-(benzyloxy)phenyl]sulfonyl}(cyclohexyloxy)amino]-2-hydroxypropylcarbamate

HRID 29206

Reaktionsgleichung

Reaktionsgleichung von HRID 29206
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([S:15](Cl)(=[O:17])=[O:16])=[CH:11][CH:10]=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>CN(C)C1C=CN=CC=1.O1CCCC1>[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:12]1[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][CH:11]=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

Komponenten

6

Edukt 3

HCID 81531DiisopropylethylamineHCID 47383854-(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

Produkt 1

HCID 59090807(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-[{[4-(benzyloxy)phenyl]sulfonyl}(cyclohexyloxy)amino]-2-hydroxypropylcarbamateAusbeute 91,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysator2×HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A mixture of 4-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), diisoproylethylamine (0.042 mL, 0.242 mmol) and 4-dimethylaminopyridine (˜1 mg) in anhydrous tetrahydrofuran (3 mL) was stirred at ambient temperature under an Argon atmosphere for 16 hours. An additional quantity of 4-benzyloxybenzenesulfonyl chloride (13 mg, 0.046 mmol) and 4-dimethylaminopyridine (˜1 mg) was added and the reaction was heated at reflux for approximately 2 hours. 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 crude product was purified on flash grade silica gel eluting with 1:1 ethyl acetate:hexane. Fractions containing the product were combined and 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-[{[4-(benzyloxy)phenyl]sulfonyl}(cyclohexyloxy)amino]-2-hydroxypropylcarbamate (143 mg, 91%). H1-NMR (chloroform-D3): 1.27 (m, 6H), 1.61 (m, 5H), 2.07 (m, 2H), 2.91 (m, 4H), 3.10 (b, 1H), 3.68 (m, 2H), 3.89 (m, 4H), 4.19 (m, 1H), 4.84 (m, 1H), 5.01 (m, 1H), 5.12 (s, 2H), 5.64 (d, 1H), 7.05 (d, 2H), 7.28 (m, 10H), 7.71 (d, 2H). MS(ESI): 703(M+Na).

Aufarbeitung

  1. temperaturethe reaction was heated
  2. temperatureat reflux for approximately 2 hours
  3. temperatureAfter cooling to ambient temperature
  4. customthe reaction mixture was partitioned between ethyl acetate and aqueous hydrochloric acid
  5. customThe phases were separated
  6. washthe organic layer was then washed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. customThe crude product was purified on flash grade silica gel eluting with 1:1 ethyl acetate
  11. additionFractions containing the product
  12. customevaporated in vacuo
  13. customdried under high vacuum

Quellen und Nachweise

ORD-Eintrag
ord-3d43f2367c0e43ceb6120dadc59c1ae2
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07419967B2

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