Reaction #670648

Reaction equation

hexane

butyl lithium

4-bromoveratrole

tetrahydrofuran

4-cyanopyridine

tetrahydrofuran

→

4-(3,4-Dimethoxybenzoyl)pyridine

Conditions

Workup

1. 1
   Otherthe reaction was carefully quenched with hydrochloric acid (45 mL, 1N)
2. 2
   workup.STIRRINGThe mixture was stirred for 30 minutes at room temperature
3. 3
   ExtractionThe mixture was extracted with ether (3×50 mL)
4. 4
   WashThe combined ethereal extracts were washed with brine (100 mL)
5. 5
   Dryingthen dried over magnesium sulfate
6. 6
   Concentrationconcentrated in vacuo to a brown solid
7. 7
   OtherThe crude product was purified by flash column chromatography (silica gel, 3% methanol/methylene chloride)
8. 8
   Otherto afford after vacuum
9. 9
   Dryingdrying (60° C., 1 mm) 1.9 g (39%) of the product

Procedure

A hexane solution of butyl lithium (9 mL, 22 mmol, 2.5M) was slowly added to a stirring solution of 4-bromoveratrole (2.9 mL, 20 mmol) in 40 mL of tetrahydrofuran under nitrogen at -70° C. After 15 minutes a solution of 4-cyanopyridine in 12 mL of tetrahydrofuran was added to the reaction mixture and stirring was continued for 45 minutes. The reaction was then allowed to warm to -10° C. and the reaction was carefully quenched with hydrochloric acid (45 mL, 1N). The mixture was stirred for 30 minutes at room temperature. The pH was then adjusted to 12 with 50 mL of a 10% aqueous solution of sodium hydroxide. The mixture was extracted with ether (3×50 mL). The combined ethereal extracts were washed with brine (100 mL) then dried over magnesium sulfate and concentrated in vacuo to a brown solid. The crude product was purified by flash column chromatography (silica gel, 3% methanol/methylene chloride) to afford after vacuum drying (60° C., 1 mm) 1.9 g (39%) of the product: mp 117-118° C.; 1H NMR (CDCl3) δ 8.85-8.76 (m, 2H), 7.60-7.50 (m, 3H), 7.40-7.30 (m, 1H), 6.97-6.88 (m, 1H), 3.98 (s, 3H), 3.96 (s, 3H); 13C NMR (CDCl3) δ 193.7, 153.9, 150.1, 149.3, 145.2, 128.7, 125.9, 122.6, 111.5, 109.9, 56.1, 56.0; Anal. Calcd for C14H13NO3. Theoretical: C, 69.12; H, 5.39; N, 5.76. Found: C, 69.05; H, 5.39; N, 5.85.

Source