4-Cyanopyridine → 4-(3,4-Dimethoxybenzoyl)pyridine

HRID 366624Notes

Reaction equation

HRID 366624 reaction equation
CCCCCC.C([Li])CCC.Br[C:13]1[CH:14]=[C:15]([O:21][CH3:22])[C:16]([O:19][CH3:20])=[CH:17][CH:18]=1.[C:23]([C:25]1[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=1)#N.[O:31]1CCCC1>>[CH3:22][O:21][C:15]1[CH:14]=[C:13]([CH:18]=[CH:17][C:16]=1[O:19][CH3:20])[C:23]([C:25]1[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=1)=[O:31]

Participants

6

Reactant 5

HCID 75064-CyanopyridineHCID 8028Tetrahydrofuran2×HCID 8058HexaneHCID 76114Benzene, 4-bromo-1,2-dimethoxy-HCID 178418339Butyllithium

Product 1

HCID 215846084-(3,4-Dimethoxybenzoyl)pyridine

Conditions

Temperature
-10 °C

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, 2 H), 7.60-7.50 (m, 3 H), 7.40-7.30 (m, 1 H), 6.97-6.88 (m, 1 H), 3.98 (s, 3 H), 3.96 (s, 3 H); 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.

Workup

  1. customthe reaction was carefully quenched with hydrochloric acid (45 mL, 1N)
  2. stirringThe mixture was stirred for 30 minutes at room temperature
  3. extractionThe mixture was extracted with ether (3×50 mL)
  4. washThe combined ethereal extracts were washed with brine (100 mL)
  5. dry with materialthen dried over magnesium sulfate
  6. concentrationconcentrated in vacuo to a brown solid
  7. customThe crude product was purified by flash column chromatography (silica gel, 3% methanol/methylene chloride)
  8. customto afford after vacuum
  9. dry with materialdrying (60° C., 1 mm) 1.9 g (39%) of the product

Sources & evidence

ORD record
ord-aa79e9e709014b73812d49d9ab07beb5
Source dataset
uspto-grants-2000_10
Patent number
US06130226

Reaction notes

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