Methyl chloroformate → 2-Propynoic acid, 3-(4-fluorophenyl)-, methyl ester

A solution of 1-(4-fluorophenyl)-2-trimethylsilylacetylene (64 g, 0.33 mol) in dry diethyl ether (400 mL) was cooled to 0° C. under a nitrogen atmosphere. To this solution was added, dropwise over 45 minutes, a solution of tetrabutylammonium fluoride (1M in tetrahydrofuran, 330 mL, 0.33 mol) via a dropping funnel maintaining the internal temperature below 2° C. The mixture was allowed to warm to room temperature over about 1 hour. Diethyl ether (300 mL) was added to the mixture and the organic solution was washed with water, saturated brine and then dried over anhydrous magnesium sulfate. The magnesium sulfate was removed by filtration and the filtrate was cooled to about −78° C. n-Butyl lithium (1.6M in hexanes, 450 mL, 0.72 mol) was added dropwise via a dropping funnel over about 1 hour while the temperature was maintained below −66° C. After complete addition the mixture was stirred at −78° C. for about 1 hour and then a precooled solution of methyl chloroformate (110 mL, 1.4 mol) in dry diethyl ether (200 mL) was added in a continuous stream as fast as possible. The mixture was allowed to cool to −78° C. and the allowed to warm to room temperature over 1.5 h. The organic reaction mixture was washed with water and saturated brine and then dried over anhydrous magnesium sulfate. The solvents are remove under reduced pressure and the residue dried under reduced pressure to give the title compound as a brown solid, 36.5 g (61%). 1H NMR (CDCl3) δ 7.58 (dd, 2H, J=9, 5.4 Hz), 7.07 (t, 2H, J=8.5 Hz), 3.84 (s, 3H). MS (+ve ion electrospray) 178 (30), (M+).

1. additionTo this solution was added, dropwise over 45 minutes
2. washthe organic solution was washed with water, saturated brine
3. dry with materialdried over anhydrous magnesium sulfate
4. customThe magnesium sulfate was removed by filtration
5. additionwas added dropwise via a dropping funnel over about 1 hour while the temperature
6. temperaturewas maintained below −66° C
7. additionAfter complete addition the mixture
8. temperatureto cool to −78° C.
9. temperatureto warm to room temperature over 1.5 h
10. washThe organic reaction mixture was washed with water and saturated brine
11. dry with materialdried over anhydrous magnesium sulfate
12. customThe solvents are remove under reduced pressure
13. customthe residue dried under reduced pressure

ORD record

ord-0cd69eb9be974207ba1a30e0bc51f546

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07109209B2