Potassium Carbonate → 2-Chloro-5-(4-(difluoromethoxy)phenyl)pyrimidine

HRID 2067882Notes

Reaction equation

HRID 2067882 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[F:9][CH:10]([F:27])[O:11][C:12]1[CH:17]=[CH:16][C:15](B2OC(C)(C)C(C)(C)O2)=[CH:14][CH:13]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.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:8][C:5]1[N:4]=[CH:3][C:2]([C:15]2[CH:16]=[CH:17][C:12]([O:11][CH:10]([F:27])[F:9])=[CH:13][CH:14]=2)=[CH:7][N:6]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 6066655-Bromo-2-chloropyrimidineHCID 220323032-(4-(Difluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 581719302-Chloro-5-(4-(difluoromethoxy)phenyl)pyrimidine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 5-bromo-2-chloropyrimidine 4 (7.7 mmol) in 1,4-dioxane (1.5 mL) is added 2-(4-(difluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 7 (8.9 mmol), 1.8M K2CO3 aq. (16.2 mmol) and Pd(PPh3)4 (0.38 mmol). The reaction is evacuated and backfilled with nitrogen twice then heated at 150° C. for 10 min under microwave. After this time, the reaction mixture is diluted with a saturated solution of NH4Cl and extracted with DCM (3×50 mL). The organic layer is washed with brine, dried over Na2SO4 and concentrated. Purification by short silica gel chromatography using a hexane:EtOAc=3:1 mixture affords 2-chloro-5-(4-(difluoromethoxy)phenyl)pyrimidine 30. 1HNMR (400 MHz, CDCl3) δ 8.73 (s, 2H), 7.47-7.52 (m, 2H), 7.20-7.24 (m, 2H), 6.52 (t, J=72 Hz, 1H). MS (m/z) (M+1)+: 257.0.

Workup

  1. customThe reaction is evacuated
  2. additionAfter this time, the reaction mixture is diluted with a saturated solution of NH4Cl
  3. extractionextracted with DCM (3×50 mL)
  4. washThe organic layer is washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customPurification by short silica gel chromatography

Sources & evidence

ORD record
ord-84af6fd6e3034739b31d6e2963cf6dad
Source dataset
uspto-grants-2012_10
Patent number
US08293757B2

Reaction notes

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