Acetic Acid → 3-Fluoro-2-vinyl-isonicotinic acid methyl ester

HRID 1426285Notes

Reaction equation

HRID 1426285 reaction equation
[F:1][C:2]1[C:10]([CH:11]=[CH2:12])=[N:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[CH3:13][Si](C=[N+]=[N-])(C)C.CCOCC.C(O)(=O)C>CO>[F:1][C:2]1[C:10]([CH:11]=[CH2:12])=[N:9][CH:8]=[CH:7][C:3]=1[C:4]([O:6][CH3:13])=[O:5]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 3283Diethyl EtherHCID 167693TrimethylsilyldiazomethaneHCID 696734763-Fluoro-2-vinylisonicotinic acid

Product 1

HCID 696727743-Fluoro-2-vinyl-isonicotinic acid methyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 3-fluoro-2-vinylisonicotinic acid (1.3 g, 7.8 mmol, from Step 1) in methanol (20 mL) cooled to 0° C., was added dropwise 2.0M trimethylsilyldiazomethane in ether (21.6 mL, 44 mmol). When the reaction was complete, acetic acid was added dropwise to quench excess reagent and the volume of solvent was reduced in vacuo. The mixture was partitioned between saturated sodium bicarbonate solution and DCM. The aqueous portion was extracted with a total of three portions of DCM. The combined extracts were dried over sodium sulfate, decanted and concentrated and The product was used without further purification (1.4 g, 100%). 1H NMR (300 MHz, CDCl3): δ 8.47 (d, 1H), 7.62 (dd, 1H), 7.08 (ddd, 1H), 6.48 (dd, 1H), 5.65 (dd, 1H), 3.97 (s, 3H); LCMS (M+H)+: 182.0.

Workup

  1. customto quench excess reagent
  2. customThe mixture was partitioned between saturated sodium bicarbonate solution and DCM
  3. extractionThe aqueous portion was extracted with a total of three portions of DCM
  4. dry with materialThe combined extracts were dried over sodium sulfate
  5. customdecanted
  6. concentrationconcentrated
  7. customThe product was used without further purification (1.4 g, 100%)

Sources & evidence

ORD record
ord-bfc661d6c6d44221bf7e79961084d0e6
Source dataset
uspto-grants-2015_01
Patent number
US08933085B2

Reaction notes

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