Dichloromethane → HCID 67357419, compound

HRID 1965253Notes

Reaction equation

HRID 1965253 reaction equation
[CH3:1][C:2]1[O: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.[CH:17]([N:30]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:32](=[O:39])[C:31]1=[O:40])([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.ClCCl>O1CCCC1.[Cl-].[NH4+].C(OCC)(=O)C>[C:24]1([CH:17]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:30]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:32]([OH:39])([C:9]3[C:8]([OH:11])=[CH:7][C:5]4[N:6]=[C:2]([CH3:1])[O:3][C:4]=4[CH:10]=3)[C:31]2=[O:40])[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 19692771-(diphenylmethyl)-1H-indole-2,3-dioneHCID 108880735-Hydroxy-2-methylbenzoxazoleHCID 178418918HCID 178418918, compound

Product 1

HCID 67357419HCID 67357419, compoundYield 11.2%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C.) suspension of 2-methyl-1,3-benzoxazol-5-ol (Fujita, et al., Synthesis (1982):62-9) (10.3 g, 68.9 mmol) in anhydrous tetrahydrofuran (150 mL) was added isopropylmagnesium chloride (34.4 mL, 2.0 M solution in tetrahydrofuran, 68.9 mmol). The reaction mixture was stirred at 0° C. for 0.5 h, and 1-benzhydrylindoline-2,3-dione (18.8 g, 59.9 mmol) and anhydrous dichloromethane (150 mL) were added. The reaction mixture was heated at reflux for 6 days and was allowed to cool to ambient temperature. The reaction mixture was diluted with a saturated aqueous solution of ammonium chloride (200 mL) and ethyl acetate (200 mL) and the phases were separated. The aqueous phase was extracted with ethyl acetate (2×200 mL) and the combined organic solution was washed with brine (2×200 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography with hexanes/ethyl acetate (3/1), followed by recrystallization from hexanes/ethyl acetate to afford 1-(diphenylmethyl)-3-hydroxy-3-(5-hydroxy-2-methyl-1,3-benzoxazol-6-yl)-1,3-dihydro-2H-indol-2-one (3.10 g, 10%) as an off-white solid: 1H NMR (300 MHz, CDCl3) δ8.41 (br s, 1H), 7.63-7.60 (m, 2H), 7.47-7.32 (m, 10H), 7.15 (s, 1H), 7.04-6.96 (m, 1H), 6.96-6.88 (m, 1H), 6.87 (d, J=9.0 Hz, 1H), 6.41 (d, 7.8 Hz, 1H), 4.58 (br s, 1H), 2.44 (s, 3H); MS (ES+) m/z 445.2 (M−17).

Workup

  1. temperatureTo a cooled
  2. temperatureThe reaction mixture was heated
  3. temperatureat reflux for 6 days
  4. temperatureto cool to ambient temperature
  5. customthe phases were separated
  6. extractionThe aqueous phase was extracted with ethyl acetate (2×200 mL)
  7. washthe combined organic solution was washed with brine (2×200 mL)
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by column chromatography with hexanes/ethyl acetate (3/1)
  12. customfollowed by recrystallization from hexanes/ethyl acetate

Sources & evidence

ORD record
ord-4fcb2cb322e3429aa5579690bd0577e8
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

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