Reaktion #362616

Reaktionsgleichung

chloromethyl phenyl sulfide

N-(4'-chloro-2'-fluoro-5'-hydroxyphenyl)-3-(trifluoromethyl)glutarimide

Compound 19

N-(4'-chloro-2'-fluoro-5'-hydroxyphenyl)-3-(trifluoromethyl)glutarimide

sodium hydride

→

desired product

Ausbeute 23.0%

N-[4-chloro-2'-fluoro-5'-[(phenylthio)methoxy]phenyl]-3-(trifluoromethyl)glutarimide

Ausbeute 23.0%

Lösungsmittel

THF

THF

THF

—

pentanes

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.DISTILLATIONfreshly distilled from sodium/benzophenone)
2. 2
   TemperaturTo the suspension, cooled in an ice bath
3. 3
   workup.DISTILLATIONfreshly distilled from sodium/benzophenone) and two 1 ml rinses of dry THF
4. 4
   workup.ADDITIONwas added dropwise
5. 5
   Temperaturto warm slowly to room temperature
6. 6
   workup.STIRRINGstirred for about 24 hours
7. 7
   Temperaturwarmed to 50° C. for 54 hours
8. 8
   SonstigeThe THF was evaporated in vacuo (2-10 Torr)
9. 9
   TemperaturThe reaction was heated to 100° C. for 8 hours
10. 10
    Temperaturthen cooled to room temperature
11. 11
    Filtrationfiltered through a short pad of neutral alumina
12. 12
    Waschenrinsed with 30 ml EtOAc
13. 13
    SonstigeThe filtrate was evaporated in vacuo
14. 14
    Sonstigethe residue was dried in the vacuum oven for 12 hours (20-50 Torr, 50° C.)
15. 15
    workup.DISTILLATIONdistilled (2-10 Torr, 70° C.)
16. 16
    SonstigeThe residue was chromatographed (silica gel, 1:1 hexanes/methylene chloride)

Vorschrift

While kept under N2, 0.15 g (3.7 mmol, 60% dispersion in oil) sodium hydride was washed with pentanes (2×0.5 ml), then suspended in 2 ml of dry THF (freshly distilled from sodium/benzophenone). To the suspension, cooled in an ice bath, were added 1.1 g (3.4 mmol) of N-(4'-chloro-2'-fluoro-5'-hydroxyphenyl)-3-(trifluoromethyl)glutarimide (Compound 19) dissolved in 3.5 ml of dry THF (freshly distilled from sodium/benzophenone) and two 1 ml rinses of dry THF. The reaction was then allowed to warm to room temperature and stirred for 15 minutes. The flask was again cooled in an ice bath while a solution of chloromethyl phenyl sulfide (0.46 ml, 0.54 g, 3.4 mmol) in 3 ml dry THF was added dropwise. The reaction mixture was allowed to warm slowly to room temperature and stirred for about 24 hours, then warmed to 50° C. for 54 hours. The THF was evaporated in vacuo (2-10 Torr) and the reaction mixture was taken up in 12 ml anhydrous dimethylformamide. The reaction was heated to 100° C. for 8 hours then cooled to room temperature. The reaction mixture was suction filtered through a short pad of neutral alumina and rinsed with 30 ml EtOAc. The filtrate was evaporated in vacuo and the residue was dried in the vacuum oven for 12 hours (20-50 Torr, 50° C.). The resulting oil was vacuum distilled (2-10 Torr, 70° C.). The residue was chromatographed (silica gel, 1:1 hexanes/methylene chloride) to yield 350 mg (23% yield) of the desired product as a white solid, m.p. 108°-109.5° C.

Quelle