Реакция #168196

Уравнение реакции

2-chloro-6-cyclopentyl-4-(4-hydroxyphenyl)nicotinonitrile

product A

2-chloro-6-cyclopentyl-4-(4-hydroxyphenyl)nicotinonitrile

o-tolylboronic acid

→

2-chloro-6-cyclopentyl-4-(4-(o-tolyloxy)phenyl)nicotinonitrile

Выход 58.0%

Растворители

dichloromethane

Условия реакции

Обработка

1. 1
   ФильтрацияThe mixture was filtered through a CELITE® pad
2. 2
   Промывкаthe pad rinsed with ethyl acetate (50 mL)
3. 3
   ПромывкаThe filtrate was washed with saturated sodium bicarbonate (5 mL), water (5 mL), brine (5 mL)
4. 4
   Сушкаdried (MgSO4)
5. 5
   Концентрированиеconcentrated
6. 6
   ПромывкаSilica gel chromatography, eluting with 0-15% ethyl acetate in hexanes

Методика

A mixture of 2-chloro-6-cyclopentyl-4-(4-hydroxyphenyl)nicotinonitrile (20 mg, 0.067 mmol, product A from Step 4 of Example 2), o-tolylboronic acid (36.4 mg, 0.268 mmol), copper(II) acetate (14.59 mg, 0.080 mmol) and 4 A molecular sieves (100 mg) in dichloromethane (3 mL) was stirred at room temperature while opening to the air for 40 h. The mixture was filtered through a CELITE® pad and the pad rinsed with ethyl acetate (50 mL). The filtrate was washed with saturated sodium bicarbonate (5 mL), water (5 mL), brine (5 mL), dried (MgSO4) and concentrated. Silica gel chromatography, eluting with 0-15% ethyl acetate in hexanes, gave 2-chloro-6-cyclopentyl-4-(4-(o-tolyloxy)phenyl)nicotinonitrile as a colorless liquid (15 mg, 58% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.50 (2H, δ, J=8.53 Hz), 7.07-7.32 (5H, m), 6.91-7.03 (2H, m), 3.05-3.28 (1H, m), 2.20 (3H, s), 1.98-2.13 (2H, m), 1.60-1.91 (6H, m); MS (ES+) m/z: 389 (M+H); LC retention time: 4.578 min (analytical HPLC Method A).

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