반응 #67675

반응 방정식

acetic acid

2-methyl-1-phenylpropan-2-ylacetate

Lithium bis(trimethylsilyl)amide

(S)-ethyl 4-chloro-3-hydroxybutanoate

→

crude title compound

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

용매

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

반응 조건

후처리

1. 1
   workup.ADDITIONthe solution was gradually added dropwise to the main reaction vessel over 40 minutes
2. 2
   workup.ADDITIONthe resulting solution was gradually added dropwise to the main reaction vessel over 20 minutes
3. 3
   workup.STIRRINGby stirring for 5 hours
4. 4
   기타was gradually elevated to 0° C
5. 5
   기타Ethyl acetate (1500 ml) and purified water (1500 ml)
6. 6
   workup.ADDITIONwere added
7. 7
   workup.STIRRINGby stirring for 10 minutes
8. 8
   기타the organic layer was separated
9. 9
   세척The separated organic layer was washed successively with a saturated sodium chloride aqueous solution (1500 ml×2)
10. 10
    기타a saturated sodium bicarbonate aqueous solution (1500 ml) and purified water (1500 ml)
11. 11
    건조dried over anhydrous magnesium sulfate
12. 12
    농축concentrated under reduced pressure

실험 절차

Lithium bis(trimethylsilyl)amide (190.8 g) was dissolved in tetrahydrofuran (1400 ml) in a main reaction vessel, followed by cooling to −75° C. and nitrogen purging. 2-methyl-1-phenylpropan-2-ylacetate (219.2 g) was charged in a separate reaction vessel and was dissolved by the addition of tetrahydrofuran (300 ml), and the solution was gradually added dropwise to the main reaction vessel over 40 minutes, followed by stirring for 1 hour. (S)-ethyl 4-chloro-3-hydroxybutanoate (50 g) was added and dissolved in tetrahydrofuran (50 ml) and the resulting solution was gradually added dropwise to the main reaction vessel over 20 minutes, followed by stirring for 5 hours. Thereafter, acetic acid (124 ml) was gradually added dropwise thereto, and the temperature was gradually elevated to 0° C. Ethyl acetate (1500 ml) and purified water (1500 ml) were added thereto, followed by stirring for 10 minutes, and the organic layer was separated. The separated organic layer was washed successively with a saturated sodium chloride aqueous solution (1500 ml×2), a saturated sodium bicarbonate aqueous solution (1500 ml) and purified water (1500 ml), dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure to give the crude title compound (299.0 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.

출처