Acetic Acid → Ethyl 4-(4-cyclopropyl-1,4-diazepan-1-yl)benzoate

Temperatur

60 °C

A solution of ethyl 4-(1,4-diazepan-1-yl)benzoate (0.621 g, 2.5 mmol), (1-ethoxycyclopropoxy)trimethylsilane (2.51 mL, 12.50 mmol) and acetic acid (0.286 mL, 5.00 mmol) in tetrahydrofuran (50 mL), methanol (5 mL) was treated with sodium cyanoborohydride (0.393 g, 6.25 mmol) at 20° C. The resulting solution was stirred at 60° C. for 18 h. The reaction mixture was cooled, filtered and evaporated to dryness. 1N HCl (40 ml) and water (60 ml) were added and the solution extracted with ethyl acetate (3×50 ml). The aqueous layer was basified to pH 10 with solid potassium carbonate and extracted with ethyl acetate (4×50 ml). The organic extracts washed with saturated NaCl (50 ml) and dried over MgSO4, filtered and evaporated to dryness. The crude product was purified by silica column chromatography, eluting with a gradient of 0 to 5% MeOH in DCM. Pure fractions were evaporated to dryness to afford ethyl 4-(4-cyclopropyl-1,4-diazepan-1-yl)benzoate (0.849 g, 118%) as a colourless oil.

1. temperatureThe reaction mixture was cooled
2. filtrationfiltered
3. customevaporated to dryness
4. addition1N HCl (40 ml) and water (60 ml) were added
5. extractionthe solution extracted with ethyl acetate (3×50 ml)
6. extractionextracted with ethyl acetate (4×50 ml)
7. washThe organic extracts washed with saturated NaCl (50 ml)
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. customevaporated to dryness
11. customThe crude product was purified by silica column chromatography
12. washeluting with a gradient of 0 to 5% MeOH in DCM
13. customPure fractions were evaporated to dryness

ORD-Eintrag

ord-5ea8033f01d946058fca533261c3438e

Quelldatensatz

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07737149B2