Methanesulfonyl chloride → Methyl {1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(3,5-difluorophenyl)acetate

Temperatur

-78 °C

To a solution of 3.83 g (20.57 mmol) of methyl(3,5-difluorophenyl)acetate in 30 mL of THF was added a solution of 8.6 mL (21.51 mmol) of butyllithium (2.5M solution in hexanes) and stirred for 30 minutes at −78° C. A solution of 5.73 g (18.7 mmol) of 1-[bis(4-chlorophenyl)methyl]azetidin-3-one in 10 mL THF was added and the solution was stirred for 2 h at −78° C. Then 2.28 g (18.6 mmol) of 4-dimethylaminopyridine, 3.3 mL(l 8.7 mmol) of DIEA and 3.0 mL (37.4 mmol) of methanesulfonyl chloride was added and the solution was stirred for 1 h as it warmed from −78° C. to rt. The reaction mixture was then warmed to 45° C. and stirred for additional 2.5 h. The mixture was poured into 250 mL of ether and washed with 50 mL of aq NaHCO3. The organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography with hexanes/ethyl acetate=15:1 to afford the title compound; 1H-NMR (CDCl3) δ 3.67 (s, 3H), 3.84 (m, 2H), 4.25 (m, 2H), 4.54 (s, 1H), 6.76 (m, 1H), 6.78 (m, 2H), 7.33 (m, 3H), 7.38 (m, 2H); Mass Spectrum: m/e=474 (M+1 35Cl, 35Cl) and 476 (M+1 35Cl, 37Cl).

1. stirringthe solution was stirred for 2 h at −78° C
2. stirringthe solution was stirred for 1 h as it
3. temperaturewarmed from −78° C. to rt
4. temperatureThe reaction mixture was then warmed to 45° C.
5. stirringstirred for additional 2.5 h
6. washwashed with 50 mL of aq NaHCO3
7. dry with materialThe organic layer was dried over Na2SO4
8. concentrationconcentrated
9. customThe residue was purified by silica gel chromatography with hexanes/ethyl acetate=15:1

ORD-Eintrag

ord-7b08000781824461a2e5018a398596d0

Quelldatensatz

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07906652B2