Oxalyl chloride → Ethyl 1-(5-bromopyrimidine-2-carbonyl)-4-methylpiperidine-4-carboxylate

To a solution of 5-bromopyrimidine-2-carboxylic acid (0.150 g, 0.742 mmol) and DMF (1 drop, catalytic amount) in DCM (10 mL) was added dropwise oxalyl chloride (0.10 mL, 1.11 mmol.) at 0° C. under inert atmosphere and the mixture stirred at rt for 1 h. The solvent was evaporated under reduced pressure under an inert atmosphere and the residue taken up in THF (5 mL) followed by the addition of DIPEA (0.70 mL, 3.71 mmol) and ethyl 4-methylpiperidine-4-carboxylate hydrochloride (0.14 g, 0.89 mmol.) at 0° C. The resulting mixture was stirred at rt for 16 h. After completion of reaction (by TLC) the mixture was poured into ice cold water (100 mL), extracted with EtOAc (3×100 mL) and the combined organics washed with water and brine, dried over Na2SO4 and filtered. The solvent was evaporated under reduced pressure and the crude residue purified on silica-gel eluting with 40% EtOAc in hexane to obtain the desired product as an off white semi-solid (0.10 g, 37% yield). MS: 358.01 [M+H]+.

1. customThe solvent was evaporated under reduced pressure under an inert atmosphere
2. stirringThe resulting mixture was stirred at rt for 16 h
3. customAfter completion of reaction (by TLC) the mixture
4. extractionextracted with EtOAc (3×100 mL)
5. washthe combined organics washed with water and brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. customThe solvent was evaporated under reduced pressure
9. customthe crude residue purified on silica-gel
10. washeluting with 40% EtOAc in hexane

ORD record

ord-51c9b22be6ab4e99969e108ee2833a72

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181234B2