Diisopropylamine → HCID 15044918, compound

Temperature

-40 °C

A solution of di-isopropylamine (11.1 g, 15.4 mL, 110 mmol) in anhydrous tetrahydrofuran (100 mL) was cooled to 0° C. under a nitrogen atmosphere. A solution of n-butyl lithium in hexanes (2.5 M, 44 mL, 110 mmol) was added dropwise with stirring. The pale yellow solution was stirred for 15 minutes at 0° C., then transferred via cannula to a suspension of methoxymethyl-triphenylphosphonium chloride (37.7 g, 110 mmol) in dry tetrahydrofuran (300 mL) stirred at -20° C. After 30 minutes, the reaction mixture was cooled to -40° C. and a solution of 1-benzylpiperid-4-one (18.9 g, 18.5 mL, 100 mmol) in anhydrous tetrahydrofuran (100 mL) was added dropwise over 15 minutes. The reaction mixture was warmed gradually to ambient temperature over 23 h. The reaction mixture was then poured onto water, mixed and extracted three times with ethyl acetate. The combined organic layers were dried over magnesium sulfate and filtered; solvent was removed in vacuo. Column chromatography (ethyl acetate) gave starting piperidine (Rf =0.7, 0.5 g) and the product (Rf =0.51, 11.6 g), an orange-yellow liquid:1HNMR:7.4-7.25(m,5H), 5.8(s,1H), 3.5(s,2H), 3.45(s,3H), 2.5-2.3(m,5H), 2.05(t,2H,J=7); MS:217.

1. stirringThe pale yellow solution was stirred for 15 minutes at 0° C.
2. stirringstirred at -20° C
3. temperatureThe reaction mixture was warmed gradually to ambient temperature over 23 h
4. additionThe reaction mixture was then poured onto water
5. additionmixed
6. extractionextracted three times with ethyl acetate
7. dry with materialThe combined organic layers were dried over magnesium sulfate
8. filtrationfiltered
9. customsolvent was removed in vacuo
10. customColumn chromatography (ethyl acetate) gave

ORD record

ord-49b10fa58527468f810a19c2dafa136e

Source dataset

uspto-grants-1992_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05116846