Sodium Hydroxide → 4-(3,5-Dimethylisoxazol-4-YL)-3-methylbenzoic acid

HRID 219799노트

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HRID 219799 반응식
[CH3:1][C:2]1[C:6]([C:7]2[CH:16]=[CH:15][C:10]([C:11]([O:13]C)=[O:12])=[CH:9][C:8]=2[CH3:17])=[C:5]([CH3:18])[O:4][N:3]=1.[OH-].[Na+]>CCO.O>[CH3:1][C:2]1[C:6]([C:7]2[CH:16]=[CH:15][C:10]([C:11]([OH:13])=[O:12])=[CH:9][C:8]=2[CH3:17])=[C:5]([CH3:18])[O:4][N:3]=1

참가 물질

5

반응물 2

HCID 14798Sodium HydroxideHCID 67528922Methyl 4-(3,5-dimethylisoxazol-4-yl)-3-methylbenzoate

생성물 1

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

시약·촉매·용매 2

HCID 702Ethanol용매HCID 962Water용매

반응 조건

온도
60 °C

실험 절차

Methyl 4-bromo-3-methylbenzoate (Intermediate 17, step 1) (4 g; 17.46 mmol; 1 eq.), 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)isoxazole (4.28 g; 19.21 mmol; 1.10 eq.), potassium carbonate (12.07 g; 87.31 mmol; 5 eq.), tetrakis(triphenylphosphine)palladium(0) (2.02 g; 1.75 mmol; 0.10 eq.) were taken in Toluene (20 mL) and water (20 mL) under N2 atmosphere. The reaction mixture was degassed with N2 and then refluxed for 4 hours. The reaction mixture was cooled to RT, filtered over a pad of celite and washed with toluene (200 mL). The filtrate was concentrated to afford a brown oil which was taken up in EtOAc (250 mL). The organic layer was washed with a saturated aqueous solution of NaHCO3 solution (100 mL), water (100 mL) and brine (100 mL), dried over MgSO4 and concentrated affording methyl 4-(3,5-dimethylisoxazol-4-yl)-3-methylbenzoate (4.2 g, 99%, HPLC (Method A) Rt 3.93 min) as an orange solid, which was used without further purification. A solution of methyl 4-(3,5-dimethylisoxazol-4-yl)-3-methylbenzoate (3 g; 12.23 mmol; 1 eq.) in EtOH (90 mL) at RT was treated with sodium hydroxide (7.34 mL; 5 M; 36.69 mmol; 3 eq.). The reaction mixture was stirred at 60° C. for 1 hour. The reaction mixture was concentrated to give a brown solid which was taken up in water (100 mL) and the aqueous phase was washed twice with EtOAc. The aqueous phase was acidified with HCl cc to pH 2. Then it was concentrated until precipitation (volume divided by 2). The suspension was filtered affording the title compound as a brown solid. It was washed with diethyl ether affording the title compound as a beige solid. 1H NMR (DMSO-d6, 300 MHz) δ 13.03 (br s, 1H), 7.95 (s, 1H), 7.86-7.84 (dd, J=7.88, 1.31 Hz, 1H), 7.34-7.32 (d, J=7.88 Hz, 1H), 2.26 (s, 3H), 2.19 (s, 3H), 2.07 (s, 3H). HPLC (Method A) Rt 3.13 min (Purity: 97.1%).

후처리

  1. customwas used without further purification
  2. concentrationThe reaction mixture was concentrated
  3. customto give a brown solid which
  4. washthe aqueous phase was washed twice with EtOAc
  5. concentrationThen it was concentrated until precipitation (volume divided by 2)
  6. filtrationThe suspension was filtered

출처 및 근거

ORD 기록
ord-5edc72fc9e6f4e4ab58a7d686d49f797
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08202865B2

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