6-CHLORO-1,2-DIHYDRO-2-OXOSPIRO[4H-3,1-BENZOXAZINE-4,4'-PIPERIDINE]-1'-CARBOXYLIC ACID 1,1-DIMETHYL ETHYL ESTER synthesis

Yield:-

Steps:

3

6-Chloro-1-[2-(dimethylamino)ethyl]spiro[3, 1-benzoxazine-4,4'-piperidin]-2(1H)-one; To a solution of 0.100 g (0.283 mmol) tert-butyl 6-chloro-2-oxo-1,2-dihydro-1'H-spiro[3,1-benzoxazine-4,4'-piperidine]-1'-carboxylate (described in WO0122919 A2, and prepared also using the procedure described in “J. Med. Chem.,1983, 26(5), 657” starting from 4-chloro aniline) in 7 ml THF was added 0.025 g (0.566 mmol) NaH. After 30 minutes at RT, 0.063 g (0.566 mmol) (2-chloro-ethyl)-dimethyl-amine was added. The reaction mixture was stirred at 60° C. overnight, then poured onto an aqueous solution of NH₄Cl and extracted twice with EtOAc. The combined organic phases were dried over Na₂SO₄ and concentrated in vacuo yielded 60 mg of a white solid. This crude material was then dissolved in 5 ml CH₂Cl₂ and 1 ml of TFA was added. After 2 hours at RT, the solvent were removed under vacuo and the resulting oil was taken up in CH₂Cl₂ and washed with an aqueous solution of NaHCO₃. The organic phase was dried with Na₂SO₄ and concentrated under vacuo to afford 6-chloro-1-[2-(dimethylamino)ethyl]spiro[3,1-benzoxazine-4,4'-piperidin]-2(1H)-one as a white solid.

References:

US2007/155761,2007,A1 Location in patent:Page/Page column 15