Dichloromethane → Hydrochloric Acid

4-Methylsulfanyl-3-trifluoromethyl-phenylamine (414 mg; 2.00 mmol), 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (400 mg; 2.00 mmol) and sodium triacetoxyborohydride (1.27 g; 6.00 mmol) are suspended in dichloromethane (10 mL) and the resulting mixture is stirred for 2 days. The suspension is then diluted with dichloromethane (50 mL) and is washed with water (30 mL) and aq. sat. ammonium chloride (3×30 mL). The organic phase is dried over magnesium sulphate, filtered and concentrated under reduced pressure to deliver the desired intermediate. The crude intermediate is then dissolved in dichloromethane (5 mL) and trifluoroacetic acid is added (2.5 mL). After 90 minutes reaction time, the mixture is concentrated under reduced pressure and co-evaporated twice with dichloromethane (10 mL). The crude residue is then triturated with a 4N solution of hydrochloric acid in dioxane (5 mL) until a precipitate forms. The solid is filtered and dried under high vacuum to afford the desired product as hydrochloride (354 mg; 1.09 mmol).

1. washis washed with water (30 mL) and aq. sat. ammonium chloride (3×30 mL)
2. dry with materialThe organic phase is dried over magnesium sulphate
3. filtrationfiltered
4. concentrationconcentrated under reduced pressure
5. dissolutionThe crude intermediate is then dissolved in dichloromethane (5 mL)
6. additiontrifluoroacetic acid is added (2.5 mL)
7. customAfter 90 minutes reaction time
8. concentrationthe mixture is concentrated under reduced pressure
9. customThe crude residue is then triturated with a 4N solution of hydrochloric acid in dioxane (5 mL) until a precipitate forms
10. filtrationThe solid is filtered
11. customdried under high vacuum

ORD-Eintrag

ord-25db155dc0c0419287bd887f841bc05c

Quelldatensatz

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09096524B2