tert-Butanol → 2-[2-(4-Methoxyphenyl)ethenyl]nicotinic acid

HRID 1581673Notes

Reaction equation

HRID 1581673 reaction equation
[H-].[Na+].C(O)(C)(C)C.[CH3:8][C:9]1[N:19]=[CH:18][CH:17]=[CH:16][C:10]=1[C:11]([O:13]CC)=[O:12].[CH:20](=O)[C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=1>CN(C=O)C.O.C(O)(=O)C>[CH3:28][O:27][C:24]1[CH:25]=[CH:26][C:21]([CH:20]=[CH:8][C:9]2[N:19]=[CH:18][CH:17]=[CH:16][C:10]=2[C:11]([OH:13])=[O:12])=[CH:22][CH:23]=1

Participants

8

Reactant 4

HCID 6386tert-ButanolHCID 24758Sodium hydrideHCID 312444-MethoxybenzaldehydeHCID 74401Ethyl 2-methylnicotinate

Product 1

HCID 688974612-[2-(4-Methoxyphenyl)ethenyl]nicotinic acidYield 42%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Conditions

Temperature
80 °C

Procedure

A mixture of NaH (60% dispersion in mineral oil, 7.4 g, 0.185 mole), tert-butanol (11.12 g, 0.15 mole), and anhydrous DMF (100 mL) was carefully warmed at 80° C. until gas evolution ceased, then was cooled to 0° C. under argon. A solution of ethyl 2-methylnicotinate (7.7 mL, 0.050 mole) in anhydrous DMF (17 mL) was added dropwise over 3 min, and the reddish-orange mixture was stirred at 0° C. for 1 hr. A solution of para-anisaldehyde (7.3 mL, 0.060 mL) in anhydrous DMF (17 mL) was added dropwise over 3 min, and the reaction was allowed to warm to RT. The mixture was stirred overnight, then was poured into ice water (200 mL), and the solution was acidified to pH 6 with glacial acetic acid. The volume was adjusted to 1 L with H2O, the flask was scratched with a glass rod, and the mixture was allowed to stand at RT for several hr, then in the refrigerator overnight. The solid was collected by suction filtration and washed with H2O. Recrystallization from boiling absolute EtOH gave the title compound (5.31 g, 42%, two crops) as yellow needles: 1H NMR (250 MHz, DMSO-d6) δ 8.70 (dd, J=4.6, 1.7 Hz, 1H), 8.18 (dd, J=7.9, 1.7 Hz, 1H), 7.95 (d, J=15.8 Hz, 1H), 7.83 (d, J=15.8 Hz, 1H), 7.57 (d, J=8.7 Hz, 2H), 7.34 (dd, J=7.9, 4.6 Hz, 1H), 6.99 (d, J=8.7 Hz, 2H), 3.79 (s, 3H); MS (ES) m/e 256 (M+H)+.

Workup

  1. temperaturewas cooled to 0° C. under argon
  2. temperatureto warm to RT
  3. stirringThe mixture was stirred overnight
  4. waitto stand at RT for several hr
  5. customin the refrigerator overnight
  6. filtrationThe solid was collected by suction filtration
  7. washwashed with H2O
  8. customRecrystallization

Sources & evidence

ORD record
ord-7340c42047e6490d8b86fd522ba33e26
Source dataset
uspto-grants-2004_05
Patent number
US06730684B1

Reaction notes

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