Trifluoroacetic acid → (3R,4S)-N-Cyclopropyl-3-fluoro-1-[5-(trifluoromethyl)pyridin-2-yl]piperidin-4-amine

A solution of tert-butyl N-cyclopropyl-N-[(3R,4S)-3-fluoropiperidin-4-yl]carbamate (100 mg), 2-chloro-5-trifluoromethylpyridine (141 mg) and Et3N (78 mg) in N,N-dimethylformamide (2 mL) is heated in a microwave reactor at 130° C. for 3 h. After concentration the residue is purified by chromatography on silica gel eluting with 0% to 30% ethyl acetate/hexane to give the intermediate product [LC (method 20): tR=3.19 min; mass spectrum (APCI): m/z=404 [M+H]+]. The Boc-amine is dissolved in dichloromethane (3 mL) and trifluoroacetic acid (0.5 mL) is added and the solution is stirred at r.t. for 1 h. After concentration dichloromethane (3 mL) and 2 M NaOH (2 mL) are added and the organic layer is separated, dried over MgSO4 and concentrated to give the title compound. LC (method 20): tR=1.99 min; Mass spectrum (APCI): m/z=304 [M+H]+.

1. concentrationAfter concentration the residue
2. customis purified by chromatography on silica gel eluting with 0% to 30% ethyl acetate/hexane
3. customto give the intermediate product [LC (method 20): tR=3.19 min; mass spectrum (APCI): m/z=404 [M+H]+]
4. concentrationAfter concentration dichloromethane (3 mL) and 2 M NaOH (2 mL)
5. additionare added
6. customthe organic layer is separated
7. dry with materialdried over MgSO4
8. concentrationconcentrated

ORDレコード

ord-653083ed4c7348c4912767f381bbe50c

出典データセット

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08921398B2