Reacción #48330

Ecuación de reacción

(E)-N-(2-(1-(tert-butyldimethylsilyloxy)-3-methylcyclobutyl)ethylidene)-2-methylpropane-2-sulfinamide

2,2,6,6-Tetramethylpiperidine

1-Butyllithium

NH4Cl

2-fluoro-5-neopentylpyridine

→

N-((S)-2-(1-(tert-Butyldimethylsilyloxy)-3-methylcyclobutyl)-1-(2-fluoro-5-neopentylpyridin-3-yl)ethyl)-2-methylpropane-2-sulfinamide

Rendimiento 61.5%

Disolventes

THF

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturato warm up to 0° C. for 5 min before it
2. 2
   Temperaturawas cooled back to −78° C. again
3. 3
   workup.STIRRINGstirring
4. 4
   workup.WAITwas continued for 1 h
5. 5
   Temperaturawarmed up to RT
6. 6
   Extracciónextracted with EtOAc (3×150 ml)
7. 7
   Secadodried over MgSO4
8. 8
   Otroevaporated

Procedimiento

2,2,6,6-Tetramethylpiperidine (2.47 ml, 14.7 mmol) was dissolved in 100 ml THF and cooled to −78° C. 1-Butyllithium (5.23 ml, 13.1 mmol, 2.5M) was added and the reaction was allowed to warm up to 0° C. for 5 min before it was cooled back to −78° C. again. At this point, a solution of 2-fluoro-5-neopentylpyridine (1.75000 g, 10.5 mmol) was added dropwise and the reaction was stirred for 1 h. Next, a solution of (E)-N-(2-(1-(tert-butyldimethylsilyloxy)-3-methylcyclobutyl)ethylidene)-2-methylpropane-2-sulfinamide (3.98 g, 11.5 mmol) in THF was added dropwise and stirring was continued for 1 h. The mixture was hydrolyzed with NH4Cl in the cold, warmed up to RT extracted with EtOAc (3×150 ml), dried over MgSO4 and evaporated. N-((S)-2-(1-(tert-Butyldimethylsilyloxy)-3-methylcyclobutyl)-1-(2-fluoro-5-neopentylpyridin-3-yl)ethyl)-2-methylpropane-2-sulfinamide (3.30 g, 61.5% yield) was obtained after glass col. Chrom. (20-70% EtOAc in Hex.). Low yield due to the formation of a minor diastereomer at the NH center (approx 30%). Mixture of cis/trans at the cyclobutylring (4:1).

Fuente