反応 #426998

反応方程式

N-[1-(2-Chloro-3-fluorophenyl)meth-(E)-ylidene]-2-methylpropane-2-sulfinamide

ammonium chloride

butyllithium

diisopropylamine

methyl acetate

→

product

(S)-3-(2-Chloro-3-fluorophenyl)-3-((R)-2-methylpropane-2-sulfinylamino)propionic acid methyl ester

溶媒

THF

ethyl acetate

THF

THF

反応条件

後処理

1. 1
   workup.ADDITIONwas added
2. 2
   workup.STIRRINGthe mixture was stirred for a further thirty minutes
3. 3
   workup.STIRRINGthe mixture was stirred again for thirty minutes
4. 4
   workup.ADDITIONadded dropwise at −75° C.
5. 5
   workup.STIRRINGthe mixture was stirred at the same temperature for three hours
6. 6
   workup.STIRRINGstirred for fifteen minutes
7. 7
   その他the organic phase was removed
8. 8
   抽出the aqueous phase was extracted with ethyl acetate (2×50 ml)
9. 9
   乾燥The combined organic phases were dried (Na2SO4)
10. 10
    ろ過filtered
11. 11
    濃縮concentrated
12. 12
    その他The residue was purified by chromatography (silica gel 40-63 μm, ethyl acetate)

実験手順

To diisopropylamine (4.13 ml), dissolved in THF (200 ml), was slowly added dropwise 1.6 N butyllithium (17.55 ml) at 0° C., and then the mixture was stirred for thirty minutes. Subsequently, the mixture was cooled to −75° C. and methyl acetate (2.13 ml) dissolved in THF (5 ml) was added, and the mixture was stirred for a further thirty minutes. Then chlorotitanium triisopropoxide (56.15 ml, 1 molar in hexane) was added dropwise at the same temperature and the mixture was stirred again for thirty minutes. N-[1-(2-Chloro-3-fluorophenyl)meth-(E)-ylidene]-2-methylpropane-2-sulfinamide was dissolved in THF (10 ml) and added dropwise at −75° C., and the mixture was stirred at the same temperature for three hours. The mixture was poured onto cold saturated ammonium chloride solution and admixed with ethyl acetate, and stirred for fifteen minutes. The phase mixture was then clarified using kieselguhr, the organic phase was removed and the aqueous phase was extracted with ethyl acetate (2×50 ml). The combined organic phases were dried (Na2SO4), filtered and concentrated. The residue was purified by chromatography (silica gel 40-63 μm, ethyl acetate). This gave the product (4.1 g) with a de of 72% by NMR.

出典