Butanal → Ethyl 2,2-difluoro-3-hydroxyhexanoate

温度

25 °C

To a mechanically stirred mixture of zinc (108 g, 1.66 mol), n-butanal (100 g, 1.39 mol), CeCl3.7H2O (10.14 g, 0.027 mol) and anhydrous THF (1.3 L) at about 25° C. was added ethyl 2-bromo-2,2-difluoroacetate (SM1, 33.8 g, 0.167 mol) under N2. The mixture was stirred at about 25° C. until the reaction had initiated, then SM1 (304 g, 1.50 mol) was added dropwise at 35° C. without external heating. After the addition completed, the mixture was stirred at 20˜35° C. until n-butanal was less than 2.0%. The reaction mixture was then cooled to about 5° C. and sat. aq. NH4Cl (800 mL) was added slowly at about 5° C., and then adjust pH 3.0 with 6 N HCl. The mixture was stirred for 15 min. and then filtered through a plug of celite; the filter cake was washed once with MTBE (1 L). The combined filtrate was then separated and the aqueous layer was extracted once with MTBE (1 L). The combined organic layers were washed once with sat. aq. NaHCO3 (1 L), once with sat. aq. NH4Cl (1 L) and then concentrated at <50° C. under reduced pressure to give 281 g of crude IM1 with 80% GC purity. The crude IM1 was purified by vacuum distillation to provide 160 g IM1 with 98% GC purity in 58% GC total yield.

1. additionSM1 (304 g, 1.50 mol) was added dropwise at 35° C. without external heating
2. additionAfter the addition
3. temperatureThe reaction mixture was then cooled to about 5° C.
4. stirringThe mixture was stirred for 15 min.
5. filtrationfiltered through a plug of celite
6. washthe filter cake was washed once with MTBE (1 L)
7. customThe combined filtrate was then separated
8. extractionthe aqueous layer was extracted once with MTBE (1 L)
9. washThe combined organic layers were washed once with sat. aq. NaHCO3 (1 L), once with sat. aq. NH4Cl (1 L)
10. concentrationconcentrated at <50° C. under reduced pressure
11. customto give 281 g of crude IM1 with 80% GC purity
12. distillationThe crude IM1 was purified by vacuum distillation
13. customto provide 160 g IM1 with 98% GC purity in 58% GC total yield

ORDレコード

ord-516ba24d6dc64720993d873a51f1e74a

出典データセット

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08846958B2