Water → 6-Fluoro-3,4-dimethoxy-2-(2-pyridyl)benzonitrile

HRID 1582385Notes

Reaction equation

HRID 1582385 reaction equation
[Cl-].[N:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[Zn+].Br[C:10]1[C:17]([O:18][CH3:19])=[C:16]([O:20][CH3:21])[CH:15]=[C:14]([F:22])[C:11]=1[C:12]#[N:13].O>C1COCC1.CN(C=O)C.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:22][C:14]1[C:11]([C:12]#[N:13])=[C:10]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][N:2]=2)[C:17]([O:18][CH3:19])=[C:16]([O:20][CH3:21])[CH:15]=1

Participants

7

Reactant 3

HCID 962WaterHCID 227212132-Bromo-6-fluoro-3,4-dimethoxybenzonitrileHCID 178479831HCID 178479831, compound

Product 1

HCID 98138056-Fluoro-3,4-dimethoxy-2-(2-pyridyl)benzonitrileYield 94.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
98 °C

Procedure

A mixture of pyridyl zinc chloride (max 31.5 mmol, prepared from 2-bromopyridine by bromine to magnesium to zinc exchange) in THF (30 ml) and 2-bromo-6-fluoro-3,4-dimethoxybenzonitrile (prepared according to step (d), 3.30 g, 12.7 mmol) in DMF (75 ml) was charged with tetrakis(triphenylphosphine)palladium(0) (0.59 g, 0.51 mmol), warmed to 98° C. and maintained at this temperature for 15 hours. After this time, the reaction mixture was cooled to room temperature and water (300 ml) added. The resulting mixture was extracted with ethyl acetate (3×150 ml), and the combined organics dried over MgSO4 before being concentrated in vacuo. The crude product was purified on silica gel (eluting with hexane/ethyl acetate [7/3 followed by 1/1] to give 3.1 g of the title product (93%).

Workup

  1. temperaturemaintained at this temperature for 15 hours
  2. temperatureAfter this time, the reaction mixture was cooled to room temperature
  3. extractionThe resulting mixture was extracted with ethyl acetate (3×150 ml)
  4. dry with materialthe combined organics dried over MgSO4
  5. concentrationbefore being concentrated in vacuo
  6. customThe crude product was purified on silica gel (
  7. washeluting with hexane/ethyl acetate [7/3 followed by 1/1]

Sources & evidence

ORD record
ord-2be419c3b1b049248d08cee6e83eefc6
Source dataset
uspto-grants-2004_05
Patent number
US06734303B2

Reaction notes

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