Potassium Carbonate → 4-(3,5-Dimethylisoxazol-4-YL)-3-methylbenzoic acid

HRID 1950819ノート

反応式

HRID 1950819 の反応式
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8]C)=[O:7])=[CH:4][C:3]=1[CH3:12].[CH3:13][C:14]1[C:18](B2OC(C)(C)C(C)(C)O2)=[C:17]([CH3:28])[O:16][N:15]=1.C(=O)([O-])[O-].[K+].[K+].[OH-].[Na+]>C1(C)C=CC=CC=1.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>[CH3:13][C:14]1[C:18]([C:2]2[CH:11]=[CH:10][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=2[CH3:12])=[C:17]([CH3:28])[O:16][N:15]=1

参加物

8

反応物 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 27586563,5-Dimethylisoxazole-4-boronic acid pinacol esterHCID 3294148Methyl 4-bromo-3-methylbenzoate

生成物 1

HCID 532250194-(3,5-Dimethylisoxazol-4-YL)-3-methylbenzoic acid

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 1140Toluene溶媒

実験手順

A suspension of methyl 4-bromo-3-methylbenzoate (4 g; 17.5 mmol; 1 eq.), 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)isoxazole (Fluorochem 11035; 4.28 g; 19.2 mmol; 1.1 eq.), potassium carbonate (12.1 g; 87.3 mmol; 5 eq.) and Pd(PPh3)4 (2.02 g; 1.75 mmol; 0.1 eq.) in toluene (20 mL) and water (20 mL) was refluxed for 4 hours. The reaction mixture was cooled down to room temperature and filtered through a pad of Celite® which was further washed with toluene (200 mL). The filtrate was concentrated in vacuo and the residue taken up in Ethyl acetate (250 mL). The organic layer was washed with sat. aq. NaHCO3 (100 mL), water (100 mL) and brine (100 mL) then dried over magnesium sulfate and concentrated in vacuo. The residue (3 g; 12.2 mmol; 1 eq.) was taken up in EtOH (90 mL), sodium hydroxide (5M; 7.34 mL; 36.7 mmol; 3 eq.) was added and the reaction mixture was stirred at 60° C. for one hour. After concentration in vacuo, the residue was taken up in water (200 mL) and the aqueous phase was washed with Ethyl acetate then acidified to pH 2 with conc. HCl. The solution was concentrated to ca. 100 mL and the precipitate filtered off and dried. Trituration in Et2O and filtration afforded the title compound as a beige solid.

後処理

  1. temperaturewas refluxed for 4 hours
  2. filtrationfiltered through a pad of Celite® which
  3. washwas further washed with toluene (200 mL)
  4. concentrationThe filtrate was concentrated in vacuo
  5. washThe organic layer was washed with sat. aq. NaHCO3 (100 mL), water (100 mL) and brine (100 mL)
  6. dry with materialthen dried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. concentrationAfter concentration in vacuo
  9. washthe aqueous phase was washed with Ethyl acetate
  10. concentrationThe solution was concentrated to ca. 100 mL
  11. filtrationthe precipitate filtered off
  12. customdried
  13. filtrationTrituration in Et2O and filtration

出典と根拠

ORDレコード
ord-cc76690989714407a0d0727a6ad01504
出典データセット
uspto-grants-2013_03
特許番号
US08404676B2

反応ノート

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