Ethanol → Methyl 4-methyl-3-(1-(1,1,1-trifluoroprop-2-en-2-yl)phthalazin-6-yl)benzoate

HRID 422557Notes

Reaction equation

HRID 422557 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]3[CH:13]=[C:14]([CH:19]=[CH:20][C:21]=3[CH3:22])[C:15]([O:17][CH3:18])=[O:16])=[CH:9][CH:10]=2)[CH:5]=[N:4][N:3]=1.CC1(C)CC(C)OB([C:31](=[CH2:36])[C:32]([F:35])([F:34])[F:33])O1.C(O)C.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.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.COCCOC>[CH3:22][C:21]1[CH:20]=[CH:19][C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:13][C:12]=1[C:8]1[CH:7]=[C:6]2[C:11](=[CH:10][CH:9]=1)[C:2]([C:31](=[CH2:36])[C:32]([F:35])([F:34])[F:33])=[N:3][N:4]=[CH:5]2

Participants

8

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 164142704,4,6-Trimethyl-2-(3,3,3-trifluoroprop-1-en-2-yl)-1,3,2-dioxaborinaneHCID 77230175Methyl 3-(1-chlorophthalazin-6-yl)-4-methylbenzoate

Product 1

HCID 66675460Methyl 4-methyl-3-(1-(1,1,1-trifluoroprop-2-en-2-yl)phthalazin-6-yl)benzoateYield 31.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

Methyl 3-(1-chlorophthalazin-6-yl)-4-methylbenzoate (563 mg, 1800 μmol), 4,4,6-trimethyl-2-(1,1,1-trifluoroprop-2-en-2-yl)-1,3,2-dioxaborinane (799 mg, 3600 μmol), tetrakis(triphenylphosphine)palladium (208 mg, 180 μmol), ethyl alcohol (200 proof; 2000 μl), 1,2-dimethoxyethane (8000 μl), and potassium carbonate (2M aqueous solution; 2700 μl, 5400 μmol) were combined in a sealed tube and heated at 80° C. for 2 h, during which LC-MS indicated 100% conversion. The cooled reaction was diluted with CH2Cl2 and washed with saturated aqueous NaHCO3 solution and brine. The organic layer was dried (MgSO4), filtered, and concentrated in vacuo. CombiFlash purification (20% to 80% EtOAc/Hexanes) afforded methyl 4-methyl-3-(1-(1,1,1-trifluoroprop-2-en-2-yl)phthalazin-6-yl)benzoate (210 mg, 31% yield) as a golden yellow foam. MS (ES+): 373.2 (M+H)+.

Workup

  1. customThe cooled reaction
  2. washwashed with saturated aqueous NaHCO3 solution and brine
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customCombiFlash purification (20% to 80% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-26d7d9d5e9a647bf97cf573acc9d83eb
Source dataset
uspto-grants-2012_01
Patent number
US08101612B2

Reaction notes

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