Réaction #1101378

Équation de réaction

1-[3-(methyloxy)-4-nitrophenyl]-4-piperidinone

3,3-difluoropiperidine hydrochloride

acetic acid

triethylamine

Sodium triacetoxyborohydride

→

3,3-difluoro-1′-[3-(methyloxy)-4-nitrophenyl]-1,4′-bipiperidine

Rendement 68.5%

Solvants

1,2-dichloroethane

Conditions de réaction

Traitement

1. 1
   Autrethe reaction was quenched with the addition of sat'd NaHCO3
2. 2
   workup.ADDITIONThe reaction was diluted with dichloromethane
3. 3
   Autrethe layers were separated
4. 4
   ExtractionThe aqueous phase was extracted with dichloromethane
5. 5
   LavageThe combined organic layers were washed with water
6. 6
   Séchagedried over MgSO4
7. 7
   Concentrationconcentrated onto silica gel
8. 8
   AutreThe crude material was purified by flash column chromatography

Mode opératoire

A mixture of 1-[3-(methyloxy)-4-nitrophenyl]-4-piperidinone (600 mg, 2.4 mmol), commercially available 3,3-difluoropiperidine hydrochloride (753 mg, 4.8 mmol), acetic acid (0.20 mL, 3.6 mmol) and triethylamine (0.33 mL, 3.6 mmol) in 1,2-dichloroethane was stirred for 30 minutes. Sodium triacetoxyborohydride (615 mg, 2.9 mmol) was added. When LC/MS indicated the absence of starting material, the reaction was quenched with the addition of sat'd NaHCO3. The reaction was diluted with dichloromethane and the layers were separated. The aqueous phase was extracted with dichloromethane. The combined organic layers were washed with water, dried over MgSO4 and concentrated onto silica gel. The crude material was purified by flash column chromatography to give 3,3-difluoro-1′-[3-(methyloxy)-4-nitrophenyl]-1,4′-bipiperidine (584 mg, 68%). 1H NMR (400 MHz, d6-DMSO) δ 7.84 (d, J=9.6 Hz, 1H), 6.55 (dd, J=9.6 and 2.0 Hz, 1H), 6.46 (d, J=2.0 Hz, 1H), 4.04 (d, J=12.8 Hz, 1H), 3.87 (s, 3H), 2.90 (t, J=12.0 Hz, 2H), 2.72-2.60 (m, 3H), 2.47 (m under DMSO peak, 2H), 1.87-1.74 (m, 4H), 1.61-1.58 (m, 2H), 1.48-1.38 (m, 2H).

Source