sodium;(E)-7-[3-(4-fluorophenyl)-1-propan-2-ylindol-2-yl]-3,5-dihydroxyhept-6-enoate → Fluvastatin acid

HRID 1268698

Reaktionsgleichung

Reaktionsgleichung von HRID 1268698
[CH3:1][CH:2]([N:4]1[C:12](/[CH:13]=[CH:14]/[CH:15]([OH:23])[CH2:16][CH:17]([OH:22])[CH2:18][C:19]([O-:21])=[O:20])=[C:11]([C:24]2[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=2)[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]1=2)[CH3:3].[Na+]>C(OCC)(=O)C>[CH3:3][CH:2]([N:4]1[C:12](/[CH:13]=[CH:14]\[C@@H:15]([OH:23])[CH2:16][C@@H:17]([OH:22])[CH2:18][C:19]([OH:21])=[O:20])=[C:11]([C:24]2[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=2)[C:10]2[C:5]1=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH3:1]

Komponenten

3

Edukt 1

HCID 16760425sodium;(E)-7-[3-(4-fluorophenyl)-1-propan-2-ylindol-2-yl]-3,5-dihydroxyhept-6-enoate

Produkt 1

HCID 6914285Fluvastatin acidAusbeute 87,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

7.0 g (16 mmole) of fluvastatin sodium was dissolved in 300 mL ethyl acetate and washed with 300 mL 10% (w/v) aqueous sodium hydrogen sulfate solution (pH 3). The organic phase was dried over anhydrous magnesium sulfate, filtered and the solvent removed under reduced pressure to afford 5.76 g (14.0 mmole) of fluvastatin acid. This material was dissolved in 300 mL anhydrous toluene and stirred at room temperature for 7 days, at which time analytical thin-layer chromatography using 5:1 methylene chloride:acetone eluent indicated approximately 30% conversion of the starting acid to a less polar product. The toluene was removed under reduced pressure and the reaction mixture was fractionated on 400 cc of silica gel using 5:1 methylene chloride: acetone eluent to afford, after combining, concentrating and drying of the appropriate fractions, 2.02 g (5.14 mmol, 32% overall) of fluvastatin lactone as a white foam. The 400 MHz 1H nuclear magnetic resonance (NMR) spectrum and the electrospray mass spectrum (ES-MS) were consistent with the lactone product. 1H NMR (Me2SO-d6) δ 7.7 (d, 1H), 7.4 (br s, 3H), 7.3 (m, 2H), 7.2 (t, 1H), 7.1 (t, 1H), 6.8 (t, 1H), 5.7 (dd, 1H), 5.3 (s, 1H), 5.2 (m, 1H), 4.9 (m, 1H), 4.1 (br s, 1H), 2.7 (dd, 1H), 2.4 (d, 1H), 1.8 (d, 1H), 1.7 (t, 1H), 1.57 (d, 6H). ES-MS: obsvd. m/z 394 ([MH]+).

Aufarbeitung

  1. washwashed with 300 mL 10% (w/v) aqueous sodium hydrogen sulfate solution (pH 3)
  2. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. customthe solvent removed under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-efec2012d04240b9b0b7250e7ab78936
Quelldatensatz
uspto-grants-2007_04
Patentnummer
US07199126B2

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