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

HRID 1017947Notes

Reaction equation

HRID 1017947 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, 2.5 M) 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, 1 N). 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, 1 N)
  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-8965597480e8442f8afd458145af439b
Source dataset
uspto-grants-2002_11
Patent number
US06479554B2

Reaction notes

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