Methyl 2-chloropyridine-4-carboxylate → HCID 66731965, compound

HRID 1963326Notes

Reaction equation

HRID 1963326 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[Br-].[F:13][C:14]1[CH:15]=[C:16]([CH:19]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:21]=1)[CH2:17][Zn+]>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:13][C:14]1[CH:15]=[C:16]([CH:19]=[C:20]([C:22]([F:23])([F:24])[F:25])[CH:21]=1)[CH2:17][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6]

Participants

5

Reactant 2

HCID 2736842Methyl 2-chloropyridine-4-carboxylateHCID 178505822HCID 178505822, compound

Product 1

HCID 66731965HCID 66731965, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

Methyl 2-chloroisonicotinate (3.0 g, 17.48 mmol) and Pd(PPh3)4 (0.606 g, 0.52 mmol) were dissolved in THF (50 mL) under nitrogen. Freshly prepared (3-fluoro-5-(trifluoromethyl)benzyl)zinc(II) bromide (5.41 g, 19.45 mmol) in THF (25 mL) was added to the yellow solution and the flask was warmed to 60° C. overnight. The reaction mixture was quenched by adding methanol. The solution was diluted with ethyl acetate and washed with NH4Cl and water. The organic layer was dried with Na2SO4, filtered through celite, and the solvent was evaporated. The residue was chromatographed using the Biotage equipment. Eluent ethyl acetate-heptane, started 20-80 and linear gradient until 60-40. Methyl 2-(3-fluoro-5-(trifluoromethyl)benzyl)isonicotinate (4.1 g, 75% yield) was isolated. 1H NMR (400 MHz, cdcl3) δ 3.94 (s, 3H), 4.25 (s, 2H), 7.13-7.22 (m, 2H), 7.33 (s, 1H), 7.69-7.75 (m, 2H), 8.70-8.74 (m, 1H). MS m/z 314 (M+H)+

Workup

  1. customThe reaction mixture was quenched
  2. additionby adding methanol
  3. additionThe solution was diluted with ethyl acetate
  4. washwashed with NH4Cl and water
  5. dry with materialThe organic layer was dried with Na2SO4
  6. filtrationfiltered through celite
  7. customthe solvent was evaporated
  8. customThe residue was chromatographed

Sources & evidence

ORD record
ord-b51d46fd7ad042e8a26e7229f39d2fb0
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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