2-Methyltetrahydrofuran → 5-(3,5-Dimethylisoxazol-4-yl)-3-hydroxy-7-methoxy-3-phenylindolin-2-one

HRID 1052985Notes

Reaction equation

HRID 1052985 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]3[C:13](=[C:14]([O:16][CH3:17])[CH:15]=2)[NH:12][C:11](=[O:18])[C:10]3=[O:19])=[C:5]([CH3:20])[O:4][N:3]=1.C1COCC1.[C:26]1([Mg]Br)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.CC1CCCO1>CCOC(C)=O>[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]3[C:13](=[C:14]([O:16][CH3:17])[CH:15]=2)[NH:12][C:11](=[O:18])[C:10]3([OH:19])[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[C:5]([CH3:20])[O:4][N:3]=1

Participants

6

Reactant 4

HCID 73012-MethyltetrahydrofuranHCID 8028TetrahydrofuranHCID 1176681345-(3,5-Dimethylisoxazol-4-yl)-7-methoxyindoline-2,3-dioneHCID 178418255HCID 178418255, compound

Product 1

HCID 862821745-(3,5-Dimethylisoxazol-4-yl)-3-hydroxy-7-methoxy-3-phenylindolin-2-oneYield 48%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 5-(3,5-dimethylisoxazol-4-yl)-7-methoxyindoline-2,3-dione (45 mg, 0.165 mmol) and anhydrous THF (1.5 mL) was added dropwise a solution of phenylmagnesium bromide in 2-methyltetrahydrofuran (2.9 M/L, 0.3 mL, 0.87 mmol). The reaction mixture was stirred for 3 hours at room temperature. The reaction mixture was diluted with EtOAc (30 mL), washed with saturated aqueous NH4Cl (10 mL), brine (3×10 mL), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo, purified by pre-TLC (CH2Cl2:EtOAc=3:2) to give the desired product as a light brown solid (28 mg, 48%). 1H NMR (400 MHz, DMSO-d6). δH 10.56 (s, 1H), 7.31-7.32 (m, 5H), 6.95-6.96 (m, 1H), 6.69-6.71 (m, 2H), 3.89 (s, 3H), 2.35 (s, 3H), 2.18 (s, 3H). MS (ESI) m/e [M+1]+ 351.

Workup

  1. washwashed with saturated aqueous NH4Cl (10 mL), brine (3×10 mL)
  2. dry with materialdried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. custompurified by pre-TLC (CH2Cl2:EtOAc=3:2)

Sources & evidence

ORD record
ord-4aed3ba09cb74648ae26421ddb4ccdc1
Source dataset
uspto-grants-2016_07
Patent number
US09393232B2

Reaction notes

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