Trimethylsilyldiazomethane → Methyl 2-Phenylisonicotinate

HRID 1171489Notes

Reaction equation

HRID 1171489 reaction equation
[C:1]1([C:7]2[CH:8]=[C:9]([CH:13]=[CH:14][N:15]=2)[C:10]([OH:12])=[O:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:16]1C=CC=CC=1.CO.C[Si](C=[N+]=[N-])(C)C>CCCCCC>[C:1]1([C:7]2[CH:8]=[C:9]([CH:13]=[CH:14][N:15]=2)[C:10]([O:12][CH3:16])=[O:11])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 167693Trimethylsilyldiazomethane2×HCID 27628452-Phenylisonicotinic acidHCID 21927730Benzene methanol

Product 1

HCID 12183945Methyl 2-Phenylisonicotinate

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

A solution of 2-phenylisonicotinic acid (459 mg, 2.30 mmol) in 9:1 benzene/methanol (20 mL) was cooled to 0° C., and treated with the dropwise addition of a 2.0 M hexane solution of (trimethylsilyl)diazomethane (1.15 mL, 2.30 mmol). The mixture was allowed to come to room temperature and stirred for 6 h. Analysis by TLC indicated incomplete reaction, so the mixture was treated with additional (trimethylsilyl)diazomethane solution (230 μL, 0.23 mmol), and the reaction was stirred for an additional 2 h. TLC of the mixture remained unchanged. The solvent was stripped, and the residue was partitioned between ethyl acetate and saturated sodium bicarbonate. The layers were separated, the organic phase was washed 2× with saturated sodium bicarbonate, the combined aqueous phases were extracted with ethyl acetate, and the combined organic phases were washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified over silica gel, eluting with 20% ethyl acetate/heptane, to yield 372 mg of methyl 2-phenylisonicotinate as a colorless oil. 1H NMR (400 MHz, CDCl3) δ ppm 8.83 (d, J=5.27 Hz, 1H), 8.29 (s, 1H), 8.04 (d, J=7.03 Hz, 2H), 7.77 (d, J=3.52 Hz, 1H), 7.51-7.42 (m, 3H), 3.98 (s, 3H).

Workup

  1. customto come to room temperature
  2. customreaction
  3. stirringthe reaction was stirred for an additional 2 h
  4. customthe residue was partitioned between ethyl acetate and saturated sodium bicarbonate
  5. customThe layers were separated
  6. washthe organic phase was washed 2× with saturated sodium bicarbonate
  7. extractionthe combined aqueous phases were extracted with ethyl acetate
  8. washthe combined organic phases were washed with brine
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified over silica gel
  12. washeluting with 20% ethyl acetate/heptane

Sources & evidence

ORD record
ord-fa4b79610ef343189093a43a0048f92a
Source dataset
uspto-grants-2010_11
Patent number
US07829571B2

Reaction notes

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