Реакция #167930

Уравнение реакции

water

Sodium hydride

(2R,4R)-2-methyl-1-((R)-1-phenylethyl)piperidin-4-ol

iodomethane

→

title compound

(2R,4R)-4-Methoxy-2-methyl-1-((R)-1-phenylethyl)piperidine

Растворители

DMF

Условия реакции

Обработка

1. 1
   workup.WAITAfter 1 h
2. 2
   ЭкстракцияThe aqueous phase was extracted with a 4:1 mixture of EtOAc/n-heptane (3×)
3. 3
   ПромывкаThe combined organic layers were washed with brine (3×)
4. 4
   Сушкаdried over anhydrous sodium sulfate
5. 5
   Фильтрацияfiltered
6. 6
   Концентрированиеconcentrated
7. 7
   ДругоеThe residue was purified via FCC (0-30% EtOAc/heptane)

Методика

Sodium hydride (710 mg, 17.7 mmol; 60% dispersion in mineral oil) was added to a solution of (2R,4R)-2-methyl-1-((R)-1-phenylethyl)piperidin-4-ol (1.95 g, 8.87 mmol) in DMF (47 mL) at 0° C. After 15 min, iodomethane (666 μL, 10.7 mmol) was added and the solution was allowed to warm to room temperature. After 1 h, water was slowly added at 0° C. The aqueous phase was extracted with a 4:1 mixture of EtOAc/n-heptane (3×). The combined organic layers were washed with brine (3×), dried over anhydrous sodium sulfate, filtered, and concentrated under reduce pressure. The residue was purified via FCC (0-30% EtOAc/heptane) to give the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 7.49 (d, J=7.8 Hz, 2H), 7.35 (t, J=7.6 Hz, 2 H), 7.21-7.28 (m, 1 H), 4.33 (q, J=6.8 Hz, 1 H), 3.36 (s, 3 H), 3.11-3.22 (m, 1 H), 2.59-2.71 (m, 1 H), 2.49 (dt, J=11.9, 3.8 Hz, 1 H), 1.99-2.16 (m, 2 H), 1.85 (d, J=12.1 Hz, 1 H), 1.33-1.42 (m, 1 H), 1.28 (d, J=7.1 Hz, 4 H), 1.25 (d, J=6.3 Hz, 3 H); MS (ESI+) m/z 234.2 (M+H)+; [α]25D-49.17 (c 1.0, MeOH).

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