Ethyl Acetate → Methyl 2-hydroxymethyl-2,3,3,3-tetrafluoropropanoate

온도

0 °C

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.

1. customwas reduced to -10° C.
2. stirringstirring
3. waitwas continued for a further 2 hours
4. dry with materialParaformaldehyde (100 g) (previously dried under vacuum over P2 O5)
5. temperaturewas heated to 180°-200° C.
6. customclose to -10° C
7. waitAfter 30 minutes
8. additionthe mixture was poured into a mixture of 30% aqueous hydrogen peroxide (150 ml) pH7 phosphate buffer (600 ml)
9. customcrushed ice
10. stirringwas stirred at 0° C. for 45 minutes
11. extractionThe mixture was extracted with dichloromethane (3×200 ml)
12. washThe combined extracts were washed with sodium disulphite solution
13. dry with materialdried (MgSO4)
14. concentrationconcentrated under reduced pressure
15. customto leave a yellow oil, which
16. filtrationfiltered through a thick plug of silica gel
17. concentrationwas again concentrated under reduced pressure
18. customThe crude product was purified by chromatography on silica
19. washeluting with 25% ethyl acetate in hexane
20. temperatureSubsequent heating to 65° C. under aspirator vacuum (20 mmHg)

ORD 기록

ord-51b2fe63afae4772b89b208bbb7dcd4a

출처 데이터셋

uspto-grants-1998_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US05750778