Ethyl chloroformate → (2-{5-[2-(5-Fluoro-2-methoxy-phenyl)-ethyl]-tetrahydro-furan-2-yl}-ethyl)-carbamic ethyl ester

Temperature

0 °C

Into a flame dried 20 mL vial was placed K2CO3 (239 mg, 1.73 mmol, 6.0 eq) and anhydrous THF (5.0 mL). The vial was purged with Ar(g) and then cooled in an ice bath. Ethyl chloroformate (156 mg, 1.44 mmol, 5.0 eq) was then added via syringe followed by slow addition of 14 (77 mg, 0.29 mmol, 1.0 eq) dissolved in THF (1.5 mL). The reaction was stirred at 0° C. for 0.5 hrs and then warmed to rt and allowed to stir an additional 3 hrs. The reaction was then stopped with sat. NaHCO3(aq) and extracted with EtOAc (3×20 mL). The organic layer was washed with brine and dried over Na2SO4, filtered, and concentrated under reduced pressure to yield crude product that was used in the next step of the synthesis. TLC: MeOH/CH2Cl2 (2:98, v:v), Rf 0.4; 1H NMR (CDCl3, 500 MHz) 6.87-6.82 (m, 2 H), 6.74-6.71 (m, 1 H), 4.12 (q, J=7.1 Hz, 2 H), 4.05-3.77 (m, 2 H), 3.78 (s, 3 H), 2.71-2.56 (m, 2 H), 2.08-1.51 (m, 10 H) 1.3 (t, J=7.2 Hz, 3 H). LRMS (ESI) [M+H]+ calcd for C18H27FNO4 340 found 340.

1. customInto a flame dried 20 mL
2. customThe vial was purged with Ar(g)
3. temperaturecooled in an ice bath
4. temperaturewarmed to rt
5. stirringto stir an additional 3 hrs
6. extractionextracted with EtOAc (3×20 mL)
7. washThe organic layer was washed with brine
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customto yield crude product that
12. customwas used in the next step of the synthesis

ORD record

ord-0b4d62816ea646699435e35a6f951594

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08168635B2