2-Bromopropane → (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl N-((1S,2R)-1-benzyl-3-(cyclopentyloxy)[(4-isopropoxyphenyl)sulfonyl]amino-2-hydroxypropyl)carbamate

HRID 29195Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 29195
[CH2:1]([C@H:8]([NH:29][C:30](=[O:40])[O:31][C@@H:32]1[C@H:39]2[C@H:35]([O:36][CH2:37][CH2:38]2)[O:34][CH2:33]1)[C@@H:9]([OH:28])[CH:10]([NH:17][S:18]([C:21]1[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=1)(=[O:20])=[O:19])[O:11][CH:12]1[CH2:16][CH2:15][CH2:14][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH:42]([CH3:44])[CH3:43].C(=O)([O-])[O-].[K+].[K+]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C>[CH2:1]([C@H:8]([NH:29][C:30](=[O:40])[O:31][C@@H:32]1[C@H:39]2[C@H:35]([O:36][CH2:37][CH2:38]2)[O:34][CH2:33]1)[C@@H:9]([OH:28])[CH:10]([NH:17][S:18]([C:21]1[CH:26]=[CH:25][C:24]([O:27][CH:42]([CH3:44])[CH3:43])=[CH:23][CH:22]=1)(=[O:20])=[O:19])[O:11][CH:12]1[CH2:13][CH2:14][CH2:15][CH2:16]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

6

Edukt 3

HCID 63582-BromopropaneHCID 11430Potassium CarbonateHCID 69224440(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl N-((1S,2R)-1-benzyl-3-(cyclopentyloxy)[(4-hydroxyphenyl)sulfonyl]amino-2-hydroxypropyl)carbamate

Produkt 1

HCID 69224930(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl N-((1S,2R)-1-benzyl-3-(cyclopentyloxy)[(4-isopropoxyphenyl)sulfonyl]amino-2-hydroxypropyl)carbamateAusbeute 76 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 67553Tetrabutylammonium IodideKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

(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.

Aufarbeitung

  1. temperaturewas heated to 50° C. for 3 hours
  2. concentrationThe reaction mixture was concentrated under vacuum to a residue
  3. additiondiluted with ethyl acetate (2 mL)
  4. washThe reaction was washed in distilled water
  5. dry with materialbrine, and was dried over magnesium sulfate
  6. concentrationThe dried solution was then concentrated to an oil
  7. custompurified by silica gel chromatography (2:1 hexanes/ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-667463e8c1584c04b79389610737be28
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07419967B2

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