methyl 2,3,3,3-tetrafluoropropanoate

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Dibutylboron triflate (5 g) was added to a stirred solution of methyl 2,3,3,3-tetrafluoropropionate (2.9 g) in dichloromethane at 0° C. under nitrogen. After 15 minutes, the solution was cooled to -10° C. and diisopropylethylamine (3.8 ml) was added in portions. After 30 minutes, freshly distilled acetaldehyde (2 ml) was added in small portions, keeping the temperature at -10° C. The reaction was stirred at -10° C. for 1 hour before quenching with a mixture of pH7 phosphate buffer (60 ml), aqueous hydrogen peroxide (100 vol; 15 ml) and crushed ice and stirring for 1.5 hours. The organic phase was separated and the aqueous layer further extracted with dichloromethane. The combined organic phases were washed with aquesous sodium metabisulphite and with brine, dried (MgSO4) and concentrated under reduced pressure to give a pink oil (2.2 g) which was distilled using a Kugelrohr apparatus. The fraction distilling at 40° C. (air bath temperature) and at 0.05 mmHg was collected; 1H NMR (270 MHz; CDCl3) (signals recorded for a 50:50 mixture of diastereomers) δ 1.34 (1.5H,d), 1.42 (1.5H,d), 2.2(1H,bs), 3.91(1.5H,bs), 3.94(1.5H,s), 4.35-4.52(1H,m) ppm. After 30 minutes at -10° C before quenching with a mixture of pH7 phosphate buffer (60 ml), aqueous hydrogen peroxide (100 vol; 15 ml) crushed ice stirring for 1.5 hours The organic phase was separated the aqueous layer further extracted with dichloromethane The combined organic phases were washed with aquesous sodium metabisulphite and with brine dried (MgSO4) concentrated under reduced pressure

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl 2,3,3,3-tetrafluoropropanoate (27.0 g) was dissolved in dry dichloromethane and the solution stirred under a dry nitrogen atmosphere at 0° C. A one molar solution of di-n-butylboron trifluoromethanesulfonate in dichloromethane (190 ml) was added in portions over 15 minutes. After a further 15 minutes, the temperature was reduced to -10° C. and di-isopropylethylamine (35 ml) was added in portions, then stirring was continued for a further 2 hours. Paraformaldehyde (100 g) (previously dried under vacuum over P2 O5) was heated to 180°-200° C. and the resulting formaldehyde was passed into the reaction mixture in a stream of dry nitrogen, keeping the temperature close to -10° C. After 30 minutes, the mixture was poured into a mixture of 30% aqueous hydrogen peroxide (150 ml) pH7 phosphate buffer (600 ml) and crushed ice, and was stirred at 0° C. for 45 minutes. The mixture was extracted with dichloromethane (3×200 ml). The combined extracts were washed with sodium disulphite solution, dried (MgSO4) and concentrated under reduced pressure to leave a yellow oil, which was redissolved in ethyl acetate and filtered through a thick plug of silica gel, and then was again concentrated under reduced pressure. The crude product was purified by chromatography on silica, eluting with 25% ethyl acetate in hexane. Subsequent heating to 65° C. under aspirator vacuum (20 mmHg) gave the product as a yellow oil (4.8 g); 1H NMR (270 MHz; CDCl3) δ 3.93(3H,s), 4.05-4.30(2H,m), 2.80(1H,bt) ppm. was reduced to -10° C. stirring was continued for a further 2 hours Paraformaldehyde (100 g) (previously dried under vacuum over P2 O5) was heated to 180°-200° C. close to -10° C After 30 minutes the mixture was poured into a mixture of 30% aqueous hydrogen peroxide (150 ml) pH7 phosphate buffer (600 ml) crushed ice was stirred at 0° C. for 45 minutes The mixture was extracted with dichloromethane (3×200 ml) The combined extracts were washed with sodium disulphite solution dried (MgSO4) concentrated under reduced pressure to leave a yellow oil, which filtered through a thick plug of silica gel was again concentrated under reduced pressure The crude product was purified by chromatography on silica eluting with 25% ethyl acetate in hexane Subsequent heating to 65° C. under aspirator vacuum (20 mmHg)