Methanol → HCID 11064222, compound

A solution of tert-butyl (5R)-6-cyano-5-hydroxy-3-oxohexanoate (10 g, 0.044 mol) in THF (60 mL) was stirred under nitrogen and methanol (20 mL) was added. The reaction mixture was stirred for 15 min. Ti(IV)isopropoxide (12.5 g, 0.044 mol) was added and stirred for 30 min. at room temperature. After cooling the reaction mixture to −50° C. to −55° C., sodium borohydride (1.67 g, 0.044 mol) was added in 4 portions maintaining the temperature between −50° C. and −55° C. The resulting mixture was stirred for 1 h at the same temperature. After warming the reaction mixture to RT, it was concentrated to a residue under vacuum at about 45° C. Methanol (60 mL) was added and the resulting mixture was concentrated. The resulting residue was cooled to RT, water (50 mL) was added and the resulting aqueous mixture was extracted with ethyl acetate (100 mL×2). The combined organic layer was washed with saturated ammonium chloride solution (2×50 mL), water (50 mL) and brine solution (50 mL), and concentrated to obtain the title compound. Yield: 7.5 g.

1. stirringstirred for 30 min. at room temperature
2. temperatureAfter cooling the reaction mixture to −50° C. to −55° C.
3. temperaturemaintaining the temperature between −50° C. and −55° C
4. stirringThe resulting mixture was stirred for 1 h at the same temperature
5. concentrationit was concentrated to a residue under vacuum at about 45° C
6. additionMethanol (60 mL) was added
7. concentrationthe resulting mixture was concentrated
8. temperatureThe resulting residue was cooled to RT
9. additionwater (50 mL) was added
10. extractionthe resulting aqueous mixture was extracted with ethyl acetate (100 mL×2)
11. washThe combined organic layer was washed with saturated ammonium chloride solution (2×50 mL), water (50 mL) and brine solution (50 mL)
12. concentrationconcentrated

ORD record

ord-143c9f6f71d34abc8e87416d1bc0bf23

Source dataset

uspto-grants-2007_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07232920B2