Triethylamine → HCID 19610946, compound

3-Quinuclidinyl-hydrazine dihydrochloride (D5) (0.78 g, 3.6 mmol) was suspended in dry methanol (30 ml) and methyl acetimidate hydrochloride (0.40 g, 3.65 mmol) added, followed by triethylamine (1.52 ml, 3 eq). The solution was stirred for 3 h at room temperature under N2, and then evaporated to dryness under reduced pressure at a temperature not exceeding 30° C. Anhydrous triethylorthoformate (40 ml) and anhydrous pyridine (4 ml) were added, and the suspension was stirred overnight at room temperature under N2 and then refluxed under N2 for 1.5 h. The mixture was cooled, evaporated to dryness under reduced pressure and the residue was dissolved in saturated aqueous potassium carbonate solution (40 ml). The solution was extracted with ethyl acetate (2×300 ml), the organic extracts dried (Na2SO4), filtered and evaporated to dryness under reduced pressure. The resulting oil was purified by column chromatography using neutral alumina and with gradient elution using ethyl acetate to 2% methanol in ethyl acetate. The resulting clear oil was crystallised as the dihydrochloride salt using diethyl ether/methanol solution and recrystallised in acetone/ether to afford the title compound as white crystals (110 mg, 13%), m.p. >250° C.

1. customevaporated to dryness under reduced pressure at a temperature not
2. customexceeding 30° C
3. additionAnhydrous triethylorthoformate (40 ml) and anhydrous pyridine (4 ml) were added
4. stirringthe suspension was stirred overnight at room temperature under N2
5. temperaturerefluxed under N2 for 1.5 h
6. temperatureThe mixture was cooled
7. customevaporated to dryness under reduced pressure
8. dissolutionthe residue was dissolved in saturated aqueous potassium carbonate solution (40 ml)
9. extractionThe solution was extracted with ethyl acetate (2×300 ml)
10. dry with materialthe organic extracts dried (Na2SO4)
11. filtrationfiltered
12. customevaporated to dryness under reduced pressure
13. customThe resulting oil was purified by column chromatography
14. washwith gradient elution
15. customThe resulting clear oil was crystallised as the dihydrochloride salt
16. customrecrystallised in acetone/ether

ORD record

ord-42b7ea87e99f4d99ba36ea2938ed05bf

Source dataset

uspto-grants-1999_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05981545