Sodium Carbonate → Methyl 4-(4-bromo-2,3-difluorophenyl)-2-methylnicotinate

HRID 1398371Notes

Reaction equation

HRID 1398371 reaction equation
I[C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([CH3:12])[N:5]=[CH:4][CH:3]=1.[Br:13][C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[C:16]([F:23])[C:15]=1[F:24].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.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>[Br:13][C:14]1[CH:19]=[CH:18][C:17]([C:2]2[C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([CH3:12])[N:5]=[CH:4][CH:3]=2)=[C:16]([F:23])[C:15]=1[F:24]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27732924-Bromo-2,3-difluorobenzeneboronic acidHCID 86710362Methyl 4-iodo-2-methylnicotinate

Product 1

HCID 86710363Methyl 4-(4-bromo-2,3-difluorophenyl)-2-methylnicotinateYield 44%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

In a microwave vessel, methyl 4-iodo-2-methylnicotinate (1.00 g, 3.61 mmol) was taken in a mixture of 1,4-dioxane (18 mL) and water (2 mL) under inert atmosphere. (4-bromo-2,3-difluorophenyl)boronic acid (1.03 g, 4.33 mmol) and Na2CO3 (765 mg, 7.22 mmol) were added to the reaction mixture and degassed for 5 minutes. Pd(Ph3P)4 (83 mg, 0.072 mmol) was added to the reaction mixture and heated in microwave at 110° C. for 90 min. The reaction mixture was diluted with water (150 mL) and extracted with ethyl acetate (200 mL). The organic phase was washed with brine (2×100 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (gradient of ethyl acetate and petroleum ether) to afford methyl 4-(4-bromo-2,3-difluorophenyl)-2-methylnicotinate (540 mg, 1.58 mmol, 44% yield) as a yellow liquid. LC/MS (ESI) m/e 344.0 [(M+2H)+, calcd for C14H12BrF2NO2 344.1]; LC/MS retention time (method C): tR=2.48 min.

Workup

  1. customdegassed for 5 minutes
  2. extractionextracted with ethyl acetate (200 mL)
  3. washThe organic phase was washed with brine (2×100 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography (gradient of ethyl acetate and petroleum ether)

Sources & evidence

ORD record
ord-ef21628a521f46eb9062a224fb7da802
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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