Methanol → Methyl 6-phenylnicotinate

HRID 1054100Notes

Reaction equation

HRID 1054100 reaction equation
[C:1]1([C:7]2[CH:14]=[CH:13][C:10]([CH:11]=[O:12])=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1C(=O)N(I)[C:17](=[O:18])C1.C([O-])([O-])=O.[K+].[K+].CO.[O-]S([O-])(=S)=O.[Na+].[Na+]>C(#N)C>[C:1]1([C:7]2[CH:14]=[CH:13][C:10]([C:11]([O:18][CH3:17])=[O:12])=[CH:9][N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 5

HCID 887MethanolHCID 11430Potassium CarbonateHCID 24477Sodium ThiosulfateHCID 120273N-IodosuccinimideHCID 27645626-Phenylnicotinaldehyde

Product 1

HCID 13129505Methyl 6-phenylnicotinate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 43b (350 mg, 1.91 mmol) in acetonitrile (20 mL) were added NIS (1.29 g, 5.73 mmol), K2CO3 (787 mg, 5.73 mmol) and CH3OH (0.39 mL, 9.55 mmol). After stirring the reaction mixture for 15 h aqueous Na2S2O3-solution (1 g Na2S2O3 in 10 mL water) was added. The resultant mixture was extracted with a solution of 50% ether in hexane (4×20 mL). The combined organic phases were washed with brine and solvent was removed under vacuum. The crude product was purified by flash chromatography on silica-gel using a mixture of hexane/ethyl acetate (6:1) as eluent. White solid. Yield: 297 mg, 73%. 1H NMR (CDCl3, 500 MHz): δH (ppm)=3.75 (s, 3H), 7.22-7.30 (m, 3H), 7.59 (dd, J=8.5, 0.9 Hz, 1H), 7.82-7.86 (m, 2H), 8.12 (dd, J=8.5, 2.2 Hz, 1H), 9.06 (dd, J=2.2, 0.9 Hz, 1H); 13C NMR (CDCl3, 125 MHz): δC (ppm)=52.3, 119.8, 124.2, 127.3, 128.9, 129.9, 137.8, 138.3, 150.9, 160.9, 165.9; (ESI): m/z=214.02 [M+H]+.

Workup

  1. additionwas added
  2. extractionThe resultant mixture was extracted with a solution of 50% ether in hexane (4×20 mL)
  3. washThe combined organic phases were washed with brine and solvent
  4. customwas removed under vacuum
  5. customThe crude product was purified by flash chromatography on silica-gel
  6. additiona mixture of hexane/ethyl acetate (6:1) as eluent

Sources & evidence

ORD record
ord-be4162e221d84575b7e27aafdf4bc497
Source dataset
uspto-grants-2016_07
Patent number
US09394290B2

Reaction notes

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