Reaktion #219400

Reaktionsgleichung

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

n-butyllithium

sodium hydride

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

butyllithium

diisoproplyamine

→

title compound

Ausbeute 93.0%

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

Ausbeute 93.0%

Lösungsmittel

tetrahydrofuran

—

hexanes

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewas held at −78° C.
2. 2
   workup.WAITMixture was held at −78° C. for 1.5 hours
3. 3
   SonstigeReaction
4. 4
   Sonstigewas held at 0° C.
5. 5
   workup.STIRRINGwith stirring for 2 hours
6. 6
   TemperaturMixture was warmed to room temperature
7. 7
   SonstigeReaction mixture
8. 8
   Sonstigewas held at −78° C.
9. 9
   workup.STIRRINGwith stirring for 2 hours
10. 10
    Temperaturto slowly warm to room temperature
11. 11
    workup.STIRRINGMixture stirred at room temperature for 14 hours
12. 12
    SonstigeReaction
13. 13
    Sonstigewas quenched with aqueous ammonium chloride
14. 14
    ExtraktionThe mixture was extracted with ethyl acetate (2×100 mL)
15. 15
    Trocknendried (magnesium sulfate)
16. 16
    Filtrationfiltered
17. 17
    Einengenconcentrated in vacuo

Vorschrift

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.

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