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

HRID 422568Notes

Reaction equation

HRID 422568 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.O.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>[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

6

Reactant 3

HCID 2735133Sodium Carbonate MonohydrateHCID 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 70%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

A mixture of methyl 3-(1-chlorophthalazin-6-yl)-4-methylbenzoate (1.0 g, 3.2 mmol), 4,4,6-trimethyl-2-(1,1,1-trifluoroprop-2-en-2-yl)-1,3,2-dioxaborinane (0.99 g, 4.48 mmol), tetrakis(triphenylphosphine)palladium (185 mg, 0.16 mmol), and sodium carbonate monohydrate (1.2 g, 9.59 mmol) in dioxane/H2O (3:1, 12 mL) was heated in a microwave reactor at 100° C. for 80 min. The reaction mixture was partitioned between EtOAc (30 mL) and H2O (30 mL); the layers were separated, and the aqueous layer was extracted with EtOAc (2×30 mL). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The resulting dark oil was dissolved in 2% Et3N in EtOAc, evaporated onto some silica gel, and purified by flash chromatography (Biotage Si 40+S, 20-60% of 2% Et3N in EtOAc/hexanes) to provide methyl 4-methyl-3-(1-(1,1,1-trifluoroprop-2-en-2-yl)phthalazin-6-yl)benzoate (833 mg, 70% yield) as a brown solid. MS (ESI, pos. ion) m/z: 373.2 (M+1).

Workup

  1. customThe reaction mixture was partitioned between EtOAc (30 mL) and H2O (30 mL)
  2. customthe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc (2×30 mL)
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe resulting dark oil was dissolved in 2% Et3N in EtOAc
  7. customevaporated onto some silica gel
  8. custompurified by flash chromatography (Biotage Si 40+S, 20-60% of 2% Et3N in EtOAc/hexanes)

Sources & evidence

ORD record
ord-8a4b653cd1904713896cbe3d65932f0e
Source dataset
uspto-grants-2012_01
Patent number
US08101612B2

Reaction notes

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