Hydrochloric Acid → 4,4,4-Trifluoro-1,3-butanediol

2,4-Dihydroxy-1,1,1-trifluorobutane (3) is prepared by sequential reduction of ethyl 4,4,4-trifluoroacetoacetate then ethyl 3-hydroxyl-4,4,4-trifluorobutyrate. Any effective reducing agent can be used. Most preferably, the reactions are conducted as follows. To a solution of ethyl 4,4,4-trifluoroacetoacetate (1) (18.4 g, 100 mmol) in ether (200 mL) is added sodium borohydride (NaBH4) (4 g, 105 mmol) in several portions over a period of 30 min at 0°-5° C. The reaction mixture is stirred at 0°-5° C. for 1 hour and at room temperature overnight. Hydrochloric acid (10%, 100 mL) is carefully added and the solid is removed by filtration. The aqueous layer is extracted with ether (150 mL) and the combination is dried over Na2SO4, filtered and evaporated to give 18.0 g clear liquid (98%). The liquid comprises ethyl 3-hydroxy-4,4,4-trifluorobutyrate (2) (M. Tordeux and C. Wakselman, J. Fluorine Chem., 20:301-306 (1982). The solution of the liquid in ether (50 mL) is added to a suspension of lithium aluminum hydride (6 g, 0.157 mol) in ether (50 mL) at 0°-5° C. for 80 minutes. After being stirred overnight at room temperature, 100 mL of 10% HCl is very carefully added to decompose excessive lithium aluminum hydride (LiAlH4). The aqueous residue is extracted by ether or ethyl acetate (2×150 mL) and the combination dried, filtered and evaporated to afford 12.6 g clear liquid of 2,4-dihydroxy-1,1,1-trifluorobutane (FIG. 1, (3)). The above procedure was conducted and a yield of 88% obtained. The boiling point of compound (3) was 51.5°-54.0° C./0.32 mmHg. The structure was verified with 1H Nuclear Magnetic Resonance (1HNMR) as follows: (CDCl3 /TMS): δ8 6.05 (d, J=6.6 Hz, 1H, 2-OH), 4.60 (s, 1H, 4-OH), 4.03 (m, 1H, CH), 3.56 (s, 2H, 4--CH2), 1.59 (m, 2H, 3-CH2) ppm. This compound was previously described by M. Tordeux, et al., J. Fluorine Chem. 20:301-306 (1982).

1. customthe solid is removed by filtration
2. extractionThe aqueous layer is extracted with ether (150 mL)
3. dry with materialthe combination is dried over Na2SO4
4. filtrationfiltered
5. customevaporated

ORD record

ord-74b142785fd44a6d884f7e56afeacceb

Source dataset

uspto-grants-1995_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05405967