Reaction #2467955

Reaction equation

methyl 2-benzamidomethyl-3-ketobutyrate

isopropylalcohol

→

(2S,3R)-methyl-2-benzamidomethyl-3-hydroxybutyrate

Yield 105.0%

Solvents

acetonitrile

triethanolamine

Conditions

Workup

1. 1
   Otherbrought up to 37° C.
2. 2
   Otherover the course of the reaction that
3. 3
   Filtrationfiltered through a 0.25 μm syringe
4. 4
   Filtrationfilter
5. 5
   workup.ADDITIONwas added to the reaction mixture
6. 6
   workup.STIRRINGThe reaction mixture was stirred for another 15 minutes
7. 7
   Filtrationfiltered through a Celite pad (5 g in a fritted glass
8. 8
   Filtrationfilter) under vacuum
9. 9
   WashThe filter cake was washed with 20 ml ethyl acetate
10. 10
    Otherto separated
11. 11
    WashThe organic layer is washed three times with 20 ml water
12. 12
    Concentrationconcentrated on a rotary evaporator to an oil of constant weight
13. 13
    OtherAfter removal of ethyl acetate, toluene (10 ml)
14. 14
    workup.ADDITIONwas added
15. 15
    workup.DISTILLATIONdistilled under vacuum

Procedure

A 250 ml 3-neck flask with overhead stirrer was charged with methyl 2-benzamidomethyl-3-ketobutyrate (25 g), isopropylalcohol (37.5 ml) and 0.1 M triethanolamine(chloride)/0.04 M MgSO4 buffer pH7.2 (30 ml). The reaction mixture is stirred and temperature brought up to 37° C. using an oil bath. The reaction is started with the addition of 0.5 ml 19 g/L NADP-Na followed by 2.5 ml 30 g/L KRED of SEQ ID No. 10; both as solutions in 0.1 M triethanolamine (chloride)/0.04 M MgSO4 buffer pH7.2. The reaction progress was followed by taking 5 μl aliquots over the course of the reaction that were diluted with 1 ml acetonitrile, filtered through a 0.25 μm syringe filter and analyzed as described in Example 3. When the conversion exceeded 96% saturated aqueous sodium chloride (12.5 ml) was added to the reaction mixture, followed by 40 ml ethyl acetate. The reaction mixture was stirred for another 15 minutes, then filtered through a Celite pad (5 g in a fritted glass filter) under vacuum. The filter cake was washed with 20 ml ethyl acetate and the two phases of the filtrate allowed to separated. The organic layer is washed three times with 20 ml water and concentrated on a rotary evaporator to an oil of constant weight. After removal of ethyl acetate, toluene (10 ml) was added and distilled under vacuum. (2S,3R)-methyl-2-benzamidomethyl-3-hydroxybutyrate (26.47 g) was obtained as an oil containing ˜10% toluene as determined by 1H-NMR—CDCl3.

Source