1,2-Dimethoxyethane → HCID 66832249, compound

HRID 1914524Notes

Reaction equation

HRID 1914524 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][N:3]=1.[F:11][C:12]([F:23])([F:22])[C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].COCCOC>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.O>[F:11][C:12]([F:23])([F:22])[C:13]1[CH:18]=[CH:17][C:16]([C:2]2[N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][N:3]=2)=[CH:15][CH:14]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 62657Potassium Phosphate, TribasicHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 221357512-Chloropyrimidine-4-carboxylic acid

Product 1

HCID 66832249HCID 66832249, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-chloro-pyrimidine-4-carboxylic acid (2.0 g, 13 mmol), 4-trifluoromethyl phenyl boronic acid (2.4 g, 13 mmol), tetrakis(triphenylphosphine)palladium(0) (0.7 g, 0.6 mmol), potassium phosphate (5.3 g, 25 mmol), 1,2-dimethoxyethane (40 mL) and water (8 mL) was heated to 80° C. under a blanket of nitrogen in a sealed tube. After 5 h, the mixture was partitioned between water (50 mL) and ethyl acetate (50 mL). The aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic layers were discarded, and the aqueous layer was acidified with concentrated HCl to pH 2. The aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic layers were dried (MgSO4), filtered, and concentrated. The residue was purified directly by FCC to afford a white solid (1.4 g, 42%). MS (ESI): mass calcd. for C12H7F3N2O2, 268.0 m/z found, 269.0 [M+H]+.

Workup

  1. customthe mixture was partitioned between water (50 mL) and ethyl acetate (50 mL)
  2. extractionThe aqueous layer was extracted with ethyl acetate (2×50 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (2×50 mL)
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified directly by FCC

Sources & evidence

ORD record
ord-5f44b73fe5ee4a12a44f4c779c35d3a2
Source dataset
uspto-grants-2013_12
Patent number
US08614201B2

Reaction notes

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