Nicotinic Acid → 7-(Phenyloxy)-1-heptyl nicotinate

HRID 2086545Notes

Reaction equation

HRID 2086545 reaction equation
CS([O:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)(=O)=O.[C:20](O)(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[N:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C>[C:20]([O:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[N:23][CH:22]=1

Participants

6

Reactant 3

HCID 938Nicotinic AcidHCID 11430Potassium CarbonateHCID 227239427-(Phenyloxy)-1-heptyl methanesulfonate

Product 1

HCID 227239467-(Phenyloxy)-1-heptyl nicotinateYield 80.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
52.5 °C

Procedure

A solution of 7-(phenyloxy)-1-heptyl methanesulfonate (0.2 g, 0.699 mmol) and nicotinic acid (0.173 g, 1.41 mmol) in anhydrous dimethyl formamide (15 mL) was placed in a 25 mL round bottomed flask. Potassium carbonate (0.097 g, 0.702 mmol) was added to this solution and the reaction mixture was heated at 50-55° C. using an oil bath for a period of 16 hours. It was then allowed to attain room temperature diluted with ethyl acetate (40 mL) and quenched with saturated NH4Cl containing ice (20 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3×10 mL). The combined organic layer was washed with saturated NAHCO3 (3×10 mL), water (2×10 mL) and brine (2×10 mL). The organic layer was dried over Na2SO4. Removal of solvent from the dried extract under reduced pressure afforded the product 7-(phenyloxy)-1-heptyl nicotinate (0.176 g, 80.4%). The product ester from step C was analyzed yielding the following confirmatory data: 1H-NMR (CDCl3) δ 1.38-1.62 (m, 6H), 1.76-1.92 (m, 4H), 3.95 (t, 2H, J=6.45 Hz), 4.35 (t, 2H, J=6.64 Hz), 6.85-6.98 (m, 3H), 7.22-7.38 (m, 2H), 7.38 (dd, 1H, J1=7.93 Hz, J2=4.93 Hz), 8.29 (dt, 1H, J1=7.91 Hz, J2=1.92 Hz), 8.77 (dd, 1H, J1=4.83 Hz, J2=1.70 Hz) and 9.23 (d, 1H, J=2.00 Hz), 13C-NMR (CDCl3) δ 25.8, 25.9, 28.5, 28.9, 29.1, 65.4, 67.6, 114.3, 120.4, 123.2, 126.2, 129.3, 136.9, 150.8, 153.2, 158.9 and 165.2; IR (neat): 1712 cm−1; MS (ES+): 314 (M+1); Anal. Calcd. for C19H23NO3: C, 72.80; H, 7.40 and N, 4.47. Found: C, 72.94; H, 7.54 and N, 4.51.

Workup

  1. customof 16 hours
  2. customto attain room temperature
  3. customquenched with saturated NH4Cl
  4. additioncontaining ice (20 mL)
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with ethyl acetate (3×10 mL)
  7. washThe combined organic layer was washed with saturated NAHCO3 (3×10 mL), water (2×10 mL) and brine (2×10 mL)
  8. dry with materialThe organic layer was dried over Na2SO4
  9. customRemoval of solvent from the dried
  10. extractionextract under reduced pressure

Sources & evidence

ORD record
ord-6c7a73f349324ed9bbebe0dda0daac94
Source dataset
uspto-grants-2004_04
Patent number
US06727237B2

Reaction notes

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