تفاعل #219400

معادلة التفاعل

N-(3-formylpyridin-2-yl)pivalamide

n-butyllithium

sodium hydride

tert-butyl 4-(2-methoxy-2-oxoethyl)piperidine-1-carboxylate

butyllithium

diisoproplyamine

→

title compound

المردود 93.0%

tert-Butyl 4-(1-hydroxy-3-methoxy-3-oxo-1-(2-pivalamidopyridin-3-yl)propan-2-yl)piperidine-1-carboxylate

المردود 93.0%

المذيبات

tetrahydrofuran

—

hexanes

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   أخرىwas held at −78° C.
2. 2
   workup.WAITMixture was held at −78° C. for 1.5 hours
3. 3
   أخرىReaction
4. 4
   أخرىwas held at 0° C.
5. 5
   workup.STIRRINGwith stirring for 2 hours
6. 6
   درجة الحرارةMixture was warmed to room temperature
7. 7
   أخرىReaction mixture
8. 8
   أخرىwas held at −78° C.
9. 9
   workup.STIRRINGwith stirring for 2 hours
10. 10
    درجة الحرارةto slowly warm to room temperature
11. 11
    workup.STIRRINGMixture stirred at room temperature for 14 hours
12. 12
    أخرىReaction
13. 13
    أخرىwas quenched with aqueous ammonium chloride
14. 14
    استخلاصThe mixture was extracted with ethyl acetate (2×100 mL)
15. 15
    تجفيفdried (magnesium sulfate)
16. 16
    ترشيحfiltered
17. 17
    تركيزconcentrated in vacuo

الإجراء التجريبي

A solution of diisoproplyamine (6.0 mL, 43 mmol) in tetrahydrofuran (200 mL) was cooled to −78° C. A 2.5M solution of n-butyllithium in hexanes (17.0 mL, 43 mmol) was added to the mixture drop-wise. Mixture was held at −78° C. with stirring for 20 minutes. A solution of tert-butyl 4-(2-methoxy-2-oxoethyl)piperidine-1-carboxylate (9.3 g, 36 mmol) in tetrahydrofuran (35 mL) was added to the mixture drop-wise. Mixture was held at −78° C. for 1.5 hours. In a separate flask, 60% sodium hydride in mineral oil (1.57 g, 39 mmol) was washed in hexanes and then suspended in tetrahydrofuran (70 mL). Mixture was cooled to 0° C. A solution of N-(3-formylpyridin-2-yl)pivalamide (6.74 g, 33 mmol) in tetrahydrofuran (20 mL) was added to the mixture drop-wise. Reaction was held at 0° C. with stirring for 2 hours. Mixture was warmed to room temperature and then added to the butyllithium containing solution drop-wise. Reaction mixture was held at −78° C. with stirring for 2 hours. Mixture was allowed to slowly warm to room temperature. Mixture stirred at room temperature for 14 hours. Reaction was quenched with aqueous ammonium chloride. The mixture was extracted with ethyl acetate (2×100 mL). Organic extracts were combined, dried (magnesium sulfate), filtered and concentrated in vacuo. Silica gel chromatography afforded the title compound as white foam in 93% yield. (M+H)+=464.2.

المصدر