Triethylamine → (3S,5R)-benzyl 3-azido-5-fluoropiperidine-1-carboxylate

To a solution of (3R,5R)-benzyl 3-fluoro-5-hydroxypiperidine-1-carboxylate (1 eq) in 14 mL of dichloromethane was added triethyl amine (3 eq) and methanesulfonyl chloride (1.5 eq) at 0° C. The reaction mixture was allowed to stir at room temperature for 1.5 hours. The crude mixture was diluted with 120 mL of diethyl ether, washed with sat. aq. sodium bicarbonate, brine, then dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude residue was dissolved in 16 mL of NMP. Sodium azide (3.0 eq) was added and the resulting suspension was stirred at 80° C. overnight. The reaction mixture was diluted with 200 mL of EtOAc and 100 mL of hexanes, washed with water, brine, then dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography (EtOAc: hexanes=1:3) to give the titled compound (90%). LC/MS (m/z): 251.1 (MH+-28).

1. washwashed with sat. aq. sodium bicarbonate, brine
2. dry with materialdried over anhydrous MgSO4
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. dissolutionThe crude residue was dissolved in 16 mL of NMP
6. stirringthe resulting suspension was stirred at 80° C. overnight
7. washwashed with water, brine
8. dry with materialdried over anhydrous MgSO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe crude residue was purified by flash chromatography (EtOAc: hexanes=1:3)

ORD record

ord-4272bcda668c4ef4835bdc7634b32fd1

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08822497B2