Trifluoroacetic acid → Benzyl 1,2-dihydrospiro[indole-3,4'-piperidine]-1'-carboxylate

Temperatur

35 °C

A solution of phenyl hydrazine (1.29 g, 12.0 mmol) and trifluoroacetic acid (3.0 mL) in a 49/1 solution of toluene/acetonitrile (50 mL) is heated at 35° C. 4-Formyl-piperidine-1-carboxylic acid benzyl ester (2.7 g, 10.91 mmol) is dissolved in a 49/1 solution of toluene/acetonitrile (10 mL) and added dropwise to the mixture (WO2005046682). The mixture is stirred at 35° C. overnight. The resulting solution is cooled to 0° C., and methanol (5 mL) is added. NaBH4 (0.619 g, 16.38 mmol) is added slowly to the solution and the mixture is stirred for 45 min. The mixture is washed with aqueous NH4OH (6%, 25 mL) and brine (30 mL), dried over sodium sulfate, and evaporated to dryness to give a yellow solid. The crude solid is recrystallised from EtOAc to give a pale yellow solid (1.25 g, 1st crop). The mother liquor is evaporated and purified by flash chromatography, eluting with hexane:ethyl acetate (8:2) to give the title compound as a pale yellow solid (1.2 g, 2nd crop) with a total yield (2.4 g, 84%). ESI/MS m/z 323 (M+H)+.

1. additionadded dropwise to the mixture (WO2005046682)
2. temperatureThe resulting solution is cooled to 0° C.
3. stirringthe mixture is stirred for 45 min
4. washThe mixture is washed with aqueous NH4OH (6%, 25 mL) and brine (30 mL)
5. dry with materialdried over sodium sulfate
6. customevaporated to dryness
7. customto give a yellow solid
8. customThe crude solid is recrystallised from EtOAc
9. customto give a pale yellow solid (1.25 g, 1st crop)
10. customThe mother liquor is evaporated
11. custompurified by flash chromatography
12. washeluting with hexane:ethyl acetate (8:2)

ORD-Eintrag

ord-8322717fa1d54262ad32cb901b3a5e2b

Quelldatensatz

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08822486B2