methyl 2,2-difluoroacetate

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Hexamethyldisilazane (1 g, 6.2 mmol) and diethylether were taken in RBF and cooled to −78° C. under nitrogen atmosphere. n-BuLi (7.7 ml) was added and stirred for 15 mins Cyclopropyl methyl ketone (0.66 ml, 6.8 mmol) was added and stirred at −78° C. for 45 mins. At this stage methyl 2,2-difluoroacetate (1.62 ml, 18.58 mmol) was added and brought the reaction mixture to rt and allowed to stir for overnight. Reaction mixture quenched with water, ether layer separated and aqueous layer was acidified with 1N HCl. Aqueous layer extracted with diethyl ether and ether was dried over anhydrous Na2SO4. Diethyl ether was removed on rotavapour to obtain the title compound (390 mg) which was used in the next step without further purification. 1H-NMR (δ ppm, CDCl3, 400 MHz): 6.08 (s, 1H), 5.95 (t, J 54.2, 1H), 1.84-1.76 (m, 1H), 1.34-1.29 (m, 2H), 1.10-1.03 (m, 2H). was added to rt to stir for overnight Reaction mixture quenched with water, ether layer separated Aqueous layer extracted with diethyl ether and ether was dried over anhydrous Na2SO4 Diethyl ether was removed on rotavapour

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl difluoroacetate (5 g, 45 mmol) in acetonitrile (50 ml) was reacted with ethanolamine (2.66 ml, 45.4 mmol) at ambient temperature for 24 hours. The solvent was evaporated and the residual oil was purified by chromatography on silica gel, eluting with dichloromethane:methanol (96:4) then dichloromethane:methanolic ammonia (94:6) to yield 2,2-difluoro-N-(2-hydroxyethyl)acetamide (6.18 g, 98% yield): The solvent was evaporated the residual oil was purified by chromatography on silica gel eluting with dichloromethane:methanol (96:4)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Hexamethyldisilazane (1 g, 6.2 mmol) and diethylether were taken in RBF and cooled to −78° C. under nitrogen atmosphere. n-BuLi (7.7 ml) was added and stirred for 15 mins Cyclopropyl methyl ketone (0.66 ml, 6.8 mmol) was added and stirred at −78° C. for 45 mins. At this stage methyl 2,2-difluoroacetate (1.62 ml, 18.58 mmol) was added and brought the reaction mixture to rt and allowed to stir for overnight. Reaction mixture quenched with water, ether layer separated and aqueous layer was acidified with 1N HCl. Aqueous layer extracted with diethyl ether and ether was dried over anhydrous Na2SO4. Diethyl ether was removed on rotavapour to obtain the title compound (390 mg) which was used in the next step without further purification. 1H-NMR (δ ppm, CDCl3, 400 MHz): 6.08 (s, 1H), 5.95 (t, J 54.2, 1H), 1.84-1.76 (m, 1H), 1.34-1.29 (m, 2H), 1.10-1.03 (m, 2H). was added to rt to stir for overnight Reaction mixture quenched with water, ether layer separated Aqueous layer extracted with diethyl ether and ether was dried over anhydrous Na2SO4 Diethyl ether was removed on rotavapour

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Hexamethyldisilazane (1 g, 6.2 mmol) and diethylether were taken in RBF and cooled to −78° C. under nitrogen atmosphere. n-BuLi (7.7 ml) was added and stirred for 15 mins Cyclopropyl methyl ketone (0.66 ml, 6.8 mmol) was added and stirred at −78° C. for 45 mins. At this stage methyl 2,2-difluoroacetate (1.62 ml, 18.58 mmol) was added and brought the reaction mixture to rt and allowed to stir for overnight. Reaction mixture quenched with water, ether layer separated and aqueous layer was acidified with 1N HCl. Aqueous layer extracted with diethyl ether and ether was dried over anhydrous Na2SO4. Diethyl ether was removed on rotavapour to obtain the title compound (390 mg) which was used in the next step without further purification. 1H-NMR (δ ppm, CDCl3, 400 MHz): 6.08 (s, 1H), 5.95 (t, J 54.2, 1H), 1.84-1.76 (m, 1H), 1.34-1.29 (m, 2H), 1.10-1.03 (m, 2H). was added to rt to stir for overnight Reaction mixture quenched with water, ether layer separated Aqueous layer extracted with diethyl ether and ether was dried over anhydrous Na2SO4 Diethyl ether was removed on rotavapour

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl difluoroacetate (5 g, 45 mmol) in acetonitrile (50 ml) was reacted with ethanolamine (2.66 ml, 45.4 mmol) at ambient temperature for 24 hours. The solvent was evaporated and the residual oil was purified by chromatography on silica gel, eluting with dichloromethane:methanol (96:4) then dichloromethane:methanolic ammonia (94:6) to yield 2,2-difluoro-N-(2-hydroxyethyl)acetamide (6.18 g, 98% yield): The solvent was evaporated the residual oil was purified by chromatography on silica gel eluting with dichloromethane:methanol (96:4)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Hexamethyldisilazane (1 g, 6.2 mmol) and diethylether were taken in RBF and cooled to −78° C. under nitrogen atmosphere. n-BuLi (7.7 ml) was added and stirred for 15 mins Cyclopropyl methyl ketone (0.66 ml, 6.8 mmol) was added and stirred at −78° C. for 45 mins. At this stage methyl 2,2-difluoroacetate (1.62 ml, 18.58 mmol) was added and brought the reaction mixture to rt and allowed to stir for overnight. Reaction mixture quenched with water, ether layer separated and aqueous layer was acidified with 1N HCl. Aqueous layer extracted with diethyl ether and ether was dried over anhydrous Na2SO4. Diethyl ether was removed on rotavapour to obtain the title compound (390 mg) which was used in the next step without further purification. 1H-NMR (δ ppm, CDCl3, 400 MHz): 6.08 (s, 1H), 5.95 (t, J 54.2, 1H), 1.84-1.76 (m, 1H), 1.34-1.29 (m, 2H), 1.10-1.03 (m, 2H). was added to rt to stir for overnight Reaction mixture quenched with water, ether layer separated Aqueous layer extracted with diethyl ether and ether was dried over anhydrous Na2SO4 Diethyl ether was removed on rotavapour