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

HRID 29217

Reaktionsgleichung

Reaktionsgleichung von HRID 29217
[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.[CH2:31]([O:38][C:39]1[CH:44]=[CH:43][C:42]([S:45](Cl)(=[O:47])=[O:46])=[CH:41][CH:40]=1)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.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]([S:45]([C:42]1[CH:41]=[CH:40][C:39]([O:38][CH2:31][C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)=[CH:44][CH:43]=1)(=[O:47])=[O:46])[O:12][CH:13]([CH2:14][CH3:15])[CH2:16][CH3:17])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Komponenten

6

Edukt 3

HCID 81531DiisopropylethylamineHCID 47383854-(Benzyloxy)benzene-1-sulfonyl chlorideHCID 59090756(3R,3aS, 6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-[(l-ethylpropoxy)amino]-2-hydroxypropylcarbamate

Produkt 1

HCID 59090701(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-[([4-(benzyloxy)phenyl]sulfonyl}(1-ethylpropoxy)amino]-2-hydroxypropylcarbamateAusbeute 74,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 218852-DimethylaminopyridineKatalysator2×HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

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), 4-benzyloxybenzenesulphonyl chloride (134 mg, 0.474 mmol), diisoproylethylamine (0.083 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 mixture was warmed to 55° C. and an additional quantity of dimethylaminopyridine (˜2 mg) was added. After stirring for 2 hours, the reaction was evaporated in vacuo and the residue was partitioned between dichloromethane and aqueous sodium hydrogen sulfate (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 3:2 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-[{[4-(benzyloxy)phenyl]sulfonyl}(1-ethylpropoxy)amino]-2-hydroxypropylcarbamate (235 mg, 74%) as a foam. H1-NMR (chloroform-D3): 0.94 (m, 6H), 1.62 (m, 7H), 3.05 (m, 5H), 3.74 (m, 2H), 3.98 (m, 4H), 4.18 (m, 1H), 4.88 (d, 1H), 5.08 (m, 1H), 5.19 (s, 2H), 5.70 (d, 1H), 7.13 (d, 2H), 7.34 (m, 10H), 7.80 (d, 2H). MS(ESI): 691(M+Na).

Aufarbeitung

  1. temperatureThe reaction mixture was warmed to 55° C.
  2. stirringAfter stirring for 2 hours
  3. customthe reaction was evaporated in vacuo
  4. customthe residue was partitioned between dichloromethane and aqueous sodium hydrogen sulfate (1N)
  5. customAfter separating the phases
  6. extractionthe aqueous layer was extracted with dichloromethane
  7. dry with materialThe combined organic phases were dried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. customThe residue was purified on flash grade silica gel eluting with 3:2 ethyl acetate
  11. additionFractions containing the product
  12. customevaporated in vacuo
  13. customdried under high vacuum

Quellen und Nachweise

ORD-Eintrag
ord-a8cce7836032403e80e046db7d969d22
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07419967B2

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