Sodium Carbonate → 2-Chloro-3-methyl-5-(4-(trifluoromethoxy)phenyl)pyridine

HRID 1846940Notes

Reaction equation

HRID 1846940 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=1.[Cl:13][C:14]1[N:19]=[CH:18][C:17](B(O)O)=[CH:16][C:15]=1[CH3:23].C([O-])([O-])=O.[K+].[K+].C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.CCOC(C)=O.O.[NH4+].[Cl-].[Cl-].[Na+].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>[Cl:13][C:14]1[C:15]([CH3:23])=[CH:16][C:17]([C:2]2[CH:7]=[CH:6][C:5]([O:8][C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=2)=[CH:18][N:19]=1

Participants

11

Reactant 4

HCID 10340Sodium CarbonateHCID 11430Potassium CarbonateHCID 27772941-Iodo-4-(trifluoromethoxy)benzeneHCID 177502362-Chloro-3-methylpyridine-5-boronic acid

Product 1

HCID 581189822-Chloro-3-methyl-5-(4-(trifluoromethoxy)phenyl)pyridine

Reagents, catalysts & solvents 6

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 1-iodo-4-(trifluoromethoxy)benzene (288 mg, 1.0 mmol) and 6-chloro-5-methylpyridin-3-ylboronic acid (223 mg, 1.3 mmol) in DMF (2 mL) was added K2CO3 (552 mg, 4.0 mmol) and H2O (0.5 mL). The reaction mixture was stirred for 5 min under an atmosphere of dry N2. Pd(PPh3)4 (10 mg, 0.009 mmol) was added, and the resulting mixture was subjected to irradiation at 120° C. for 10 min. Cooled, diluted with EtOAc (20 mL), filtered through a layer of celite, washed with 10% DMF in EtOAc (50 mL), transferred to a separation funnel, organic phase was washed with 2N Na2CO3 (20 mL, 4.00 mmol), H2O (20 mL), 30% aqueous NH4Cl (50 mL) and brine (50 mL), and dried and concentrated. The crude mixture was subjected to preparative HPLC with a gradient MeCN/H2O (5% to 98%) containing 0.1% TFA to afford 2-chloro-3-methyl-5-(4-(trifluoromethoxy)phenyl)pyridine,

Workup

  1. customthe resulting mixture was subjected to irradiation at 120° C. for 10 min
  2. temperatureCooled
  3. filtrationfiltered through a layer of celite
  4. washwashed with 10% DMF in EtOAc (50 mL)
  5. customtransferred to a separation funnel
  6. customdried
  7. concentrationconcentrated
  8. additioncontaining 0.1% TFA

Sources & evidence

ORD record
ord-f4c8be6ded184f8dab7c0bc7da7ad145
Source dataset
uspto-grants-2015_02
Patent number
US08952034B2

Reaction notes

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