Isatin → 3-hydroxy-3-(5-hydroxy-2-methyl-1,3-benzothiazol-6-yl)-1,3-dihydro-2H-indol-2-one

HRID 1407372Notes

Reaction equation

HRID 1407372 reaction equation
[CH3:1][C:2]1[S:3][C:4]2[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][C:5]=2[N:6]=1.C([Mg]Cl)(C)C.[NH:17]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:20](=[O:21])[C:18]1=[O:19]>O1CCCC1.[Cl-].[NH4+].C(OCC)(=O)C>[OH:21][C:20]1([C:9]2[C:8]([OH:11])=[CH:7][C:5]3[N:6]=[C:2]([CH3:1])[S:3][C:4]=3[CH:10]=2)[C:22]2[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=2)[NH:17][C:18]1=[O:19]

Participants

7

Reactant 3

HCID 7054IsatinHCID 6997992-Methyl-1,3-benzothiazol-5-olHCID 178418918HCID 178418918, compound

Product 1

HCID 673568823-hydroxy-3-(5-hydroxy-2-methyl-1,3-benzothiazol-6-yl)-1,3-dihydro-2H-indol-2-oneYield 62.1%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a cooled (0° C.) solution of 2-methylbenzo[d]thiazol-5-ol (4.0 g, 24.0 mmol) in anhydrous tetrahydrofuran (50 mL) was added isopropylmagnesium chloride (2 M solution in tetrahydrofuran, 12.0 mL, 24.0 mmol). The resultant suspension was stirred at 0° C. for 0.5 h and isatin (3.1 g, 21.2 mmol) was added in one portion. The reaction mixture was stirred at ambient temperature for 48 h and was diluted with a saturated aqueous solution of ammonium chloride (80 mL) and ethyl acetate (200 mL). The phases were separated and the aqueous phase was extracted with ethyl acetate (3×50 mL). The combined organic solution was washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product was triturated with boiling ethyl acetate (10 mL), filtered and dried in vacuo to afford 3-hydroxy-3-(5-hydroxy-2-methyl-1,3-benzothiazol-6-yl)-1,3-dihydro-2H-indol-2-one (4.11 g, 62%) as an off-white microcrystalline solid: 1H NMR (300 MHz, DMSO-d6) δ10.34 (s, 1H), 10.02 (br s, 1H), 8.85 (br s, 1H), 7.78 (d, J=8.6 Hz, 1H), 7.18-7.10 (m, 1H), 7.01-6.74 (m, 4H), 2.77 (br s, 3H); MS (ES+) m/z 313.1 (M+1).

Workup

  1. customThe phases were separated
  2. extractionthe aqueous phase was extracted with ethyl acetate (3×50 mL)
  3. washThe combined organic solution was washed with brine (50 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was triturated with boiling ethyl acetate (10 mL)
  8. filtrationfiltered
  9. customdried in vacuo

Sources & evidence

ORD record
ord-721d669d7ce549d7a85ddd11674b63f6
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

Loading…