Reaction #67676

Reaction equation

sodium borohydride

hydrogen peroxide

2-methyl-1-phenylpropan-2-yl 6-chloro-5-hydroxy-3-oxohexanoate

methoxydiethylborane

→

crude title compound

Yield 4.5%

(3R,5S)-2-methyl-1-phenylpropan-2-yl 6-chloro-3,5-dihydroxy-hexanoate

Yield 4.5%

Solvents

tetrahydrofuran

methanol

Ethyl acetate

acetic acid

Conditions

Workup

1. 1
   workup.STIRRINGby stirring for 5 hours
2. 2
   TemperatureThe mixture was warmed to room temperature
3. 3
   workup.STIRRINGby stirring for 30 minutes
4. 4
   Extractionextraction
5. 5
   ExtractionThe aqueous layer was reversely extracted with ethyl acetate (1000 ml)
6. 6
   Washwashed three times with a saturated sodium bicarbonate aqueous solution (1500 ml)
7. 7
   DryingThe residue was dried over anhydrous magnesium sulfate
8. 8
   Concentrationconcentrated under reduced pressure

Procedure

The crude compound 2-methyl-1-phenylpropan-2-yl 6-chloro-5-hydroxy-3-oxohexanoate (7a, 298 g) prepared in Example 1 was dissolved in a mixed solvent of tetrahydrofuran (2000 ml) and methanol (1000 ml), and the solution was cooled to −75° C. At the same temperature, methoxydiethylborane (78.8 ml) was gradually added dropwise to this solution over 20 minutes, followed by stirring for 40 minutes. Thereafter, sodium borohydride (25.0 g) was added in 5 divided portions, followed by stirring for 5 hours, and acetic acid (96 ml) was gradually added dropwise thereto. The mixture was warmed to room temperature and allowed to stand. Ethyl acetate (1800 ml) and a 3% hydrogen peroxide aqueous solution (1500 ml) were charged to the reaction section, followed by stirring for 30 minutes and extraction. The aqueous layer was reversely extracted with ethyl acetate (1000 ml), and the organic layer was combined and washed three times with a saturated sodium bicarbonate aqueous solution (1500 ml). The residue was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to give the crude title compound (13.6 g). A portion of the crude compound was purified by silica gel column (ethyl acetate:n-hexane=3:7(v/v)) to obtain the following NMR data.

Source