Citric Acid → 3-{[(alpha-Isobutanoyloxyethoxy)carbonyl]aminomethyl]-5-Methylhexanoic Acid

Temperatur

0 °C

To a stirred suspension of pregabalin (2) (150 mg, 0.94 mmol) in anhydrous dichloromethane (10 mL) at 0° C. was added triethylamine (0.26 mL, 1.88 mmol) and trimethylchlorosilane (0.24 mL, 1.88 mmol). After stirring for 15 min at 0° C., a solution of α-isobutanoyloxyethyl-p-nitrophenyl carbonate (111) (267 mg, 0.94 mmol) in dichloromethane (3 mL) was added. The resulting mixture was stirred at room temperature for 1.5 h. The reaction mixture was acidified with citric acid and extracted with dichloromethane. The combined organic extracts were washed with brine and dried over Na2SO4. After filtration and evaporation, the crude product was purified by silica gel chromatography, eluting first with dichloromethane to remove nitrophenol, then with 30% ethyl acetate in dichloromethane to afford 130 mg (48%) of the title compound as a mixture of two diastereomers. 1H-NMR (CDCl3, 400 MHz): δ 0.90 (m, 6H), 1.70 (m, 8H), 1.46 (d, J=5.6 Hz, 3H), 1.66 (1H, m), 2.15 (m, 1H), 2.33 (m, 2H), 2.53 (m, 1H), 3.12 (m, 1H), 3.29 (m, 1H), 5.08 (t, J=6.0 Hz, 1H), 6.79 (m, 1H).

1. stirringThe resulting mixture was stirred at room temperature for 1.5 h
2. extractionextracted with dichloromethane
3. washThe combined organic extracts were washed with brine
4. dry with materialdried over Na2SO4
5. filtrationAfter filtration and evaporation
6. customthe crude product was purified by silica gel chromatography
7. washeluting first with dichloromethane
8. customto remove nitrophenol

ORD-Eintrag

ord-a889676cb49e412cba9ab6a090bcc92a

Quelldatensatz

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08367722B2