تفاعل #799396

معادلة التفاعل

hexane

NaH

methyl 1-(5-bromopyrimidin-2-yl)-4-hydroxypiperidine-4-carboxylate

MeI

→

product

المردود 57.0%

1-(5-Bromopyrimidin-2-yl)-4-methoxy-piperidine-4-carboxylic acid

المردود 57.0%

المذيبات

DMF

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe temperature of the reaction was slowly raised to rt
2. 2
   workup.WAITleft
3. 3
   workup.STIRRINGto stir for 4 h
4. 4
   درجة الحرارةThe reaction was then cooled to 0° C.
5. 5
   أخرىquenched by drop wise addition of saturated NH4Cl solution (50 mL)
6. 6
   استخلاصextracted with EtOAc (3×100 mL)
7. 7
   غسيلthe combined organics washed with brine
8. 8
   تجفيفdried (Na2SO4)
9. 9
   ترشيحfiltered
10. 10
    تركيزconcentrated under reduced pressure
11. 11
    أخرىThe crude residue was purified over 100-200 M silica-gel

الإجراء التجريبي

A solution of methyl 1-(5-bromopyrimidin-2-yl)-4-hydroxypiperidine-4-carboxylate (0.2 g, 0.63 mmol) in DMF (25 mL) was cooled to 0° C. followed by portion wise addition of NaH (60% dispersion in mineral oil, 0.05 g, 1.08 mmol) and the mixture stirred at 0° C. for 45 min followed by addition of MeI (0.20 mL, 3.16 mmol). The temperature of the reaction was slowly raised to rt and left to stir for 4 h. The reaction was then cooled to 0° C. and quenched by drop wise addition of saturated NH4Cl solution (50 mL), extracted with EtOAc (3×100 mL) and the combined organics washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The crude residue was purified over 100-200 M silica-gel using 3% EtOAc:hexane to obtain the product as an off-white solid (0.12 g, 57% yield). MS: 330.18 [M+H]+.

المصدر