Triethylamine → (R)-[4-amino-1-(3,3,3-trifluoro-2-hydroxy-2-methylpropionyl)piperidine]

To a solution of 4-t-butyloxycarbonylaminopiperidine (Method C, 8.0 g, 40.0 mmol) and triethylamine (8.5 ml), 60 mmol) in DCM (200 ml) was added a solution of (S)-3,3,3-trifluoro-2-trimethylsilyloxy-2-methylpropanoyl chloride (J. Med. Chem., 1999, 42, 2741-2746) (10.0 g, 41.3 mmol) in DCM (5 ml). The resultant mixture was stirred at ambient temperature overnight, the DCM evaporated, the residue taken up in EtOAc (150 ml), washed with saturated citric acid solution, saturated sodium hydrogen carbonate solution and brine, dried and evaporated. The residue was dissolved in methanol (25 ml), treated with saturated hydrogen chloride in methanol (100 ml), stirred at ambient temperature overnight and evaporated to dryness. The residue was recrystallized from methanol/EtOAc to give the title compound as the hydrochloride salt (7.5 g, 27.2 mmol). Mp: 245-246° C.; NMR: 1.45 (m, 2H), 1.5 (s, 3H), 1.95 (m, 2H), 3.25 (m, 1H), 4.4 (m, 2H), 4.65 (m, 2H), 7.15 (s, 1H), 8.2 (s, 3H); m/z (+ve ESP) 241 (M+H)+.

1. customthe DCM evaporated
2. washwashed with saturated citric acid solution, saturated sodium hydrogen carbonate solution and brine
3. customdried
4. customevaporated
5. dissolutionThe residue was dissolved in methanol (25 ml)
6. additiontreated with saturated hydrogen chloride in methanol (100 ml)
7. customevaporated to dryness
8. customThe residue was recrystallized from methanol/EtOAc

ORD record

ord-44f5c5c8f60140e09160b961ec0b1064

Source dataset

uspto-grants-2005_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06878712B1