Reaktion #57473

ord-667463e8c1584c04b79389610737be28

Reaktionsgleichung

O=C(N[C@@H](Cc1ccccc1)[C@@H](O)C(NS(=O)(=O)c1ccc(O)cc1)OC1CCCC1)O[C@H]1CO[C@H]2OCC[C@H]21
(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl N-((1S,2R)-1-benzyl-3-(cyclopentyloxy)[(4-hydroxyphenyl)sulfonyl]amino-2-hydroxypropyl)carbamate
CC(C)Br
2-bromopropane
O=C([O-])[O-].[K+].[K+]
potassium carbonate
→
CC(C)Oc1ccc(S(=O)(=O)NC(OC2CCCC2)[C@H](O)[C@H](Cc2ccccc2)NC(=O)O[C@H]2CO[C@H]3OCC[C@H]32)cc1
white solid
Ausbeute 76.0%
CC(C)Oc1ccc(S(=O)(=O)NC(OC2CCCC2)[C@H](O)[C@H](Cc2ccccc2)NC(=O)O[C@H]2CO[C@H]3OCC[C@H]32)cc1
(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl N-((1S,2R)-1-benzyl-3-(cyclopentyloxy)[(4-isopropoxyphenyl)sulfonyl]amino-2-hydroxypropyl)carbamate
Ausbeute 76.0%

Edukte

O=C(N[C@@H](Cc1ccccc1)[C@@H](O)C(NS(=O)(=O)c1ccc(O)cc1)OC1CCCC1)O[C@H]1CO[C@H]2OCC[C@H]21
(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl N-((1S,2R)-1-benzyl-3-(cyclopentyloxy)[(4-hydroxyphenyl)sulfonyl]amino-2-hydroxypropyl)carbamate
CC(C)Br
2-bromopropane
O=C([O-])[O-].[K+].[K+]
potassium carbonate

Reagenzien

CCCC[N+](CCCC)(CCCC)CCCC.[I-]
tetrabutylammonium iodide

Lösungsmittel

CN(C)C=O
DMF

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    Temperaturwas heated to 50° C. for 3 hours
  2. 2
    EinengenThe reaction mixture was concentrated under vacuum to a residue
  3. 3
    workup.ADDITIONdiluted with ethyl acetate (2 mL)
  4. 4
    WaschenThe reaction was washed in distilled water
  5. 5
    Trocknenbrine, and was dried over magnesium sulfate
  6. 6
    EinengenThe dried solution was then concentrated to an oil
  7. 7
    Sonstigepurified by silica gel chromatography (2:1 hexanes/ethyl acetate)

Vorschrift

(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl N-((1S,2R)-1-benzyl-3-(cyclopentyloxy)[(4-hydroxyphenyl)sulfonyl]amino-2-hydroxypropyl)carbamate (0.13 mmol, 75 mg) was combined with 2-bromopropane (0.26 mmol, 0.025 mL), potassium carbonate (0.65 mmol, 90 mg), tetrabutylammonium iodide (5 mg) and anhydrous DMF (1 mL). The reaction stirred under a nitrogen atmosphere at room temperature for 15 hours, then was heated to 50° C. for 3 hours. The reaction mixture was concentrated under vacuum to a residue and diluted with ethyl acetate (2 mL). The reaction was washed in distilled water and brine, and was dried over magnesium sulfate. The dried solution was then concentrated to an oil and purified by silica gel chromatography (2:1 hexanes/ethyl acetate) to yield 61 mg (76%) of a white solid. Rf=0.50 (2:1 hexanes/ethyl acetate); H1-NMR (CDCl3): δ 7.69 (2H,d), 7.33-7.13 (6H,m), 6.96 (2H,d), 5.65 (1H,s), 5.02 (1H,m), 4.86 (1H,m), 4.80 (1H,m), 4.65 (1H,m), 3.99-3.80 (5H,m), 3.69 (2H,m), 3.11 (1H,br.s), 3.09-2.98 (3H,m), 2.91 (1H,m), 2.83 (1H,m), 1.89-1.72 (4H,m), 1.7-1.46 (4H,m), 1.38 (6H,d). MS (ESI): M+H=619.

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US07419967B2uspto-grants-2008_09