Ethanol → HCID 71552188, compound

HRID 509455Notes

Reaction equation

HRID 509455 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:15]2[C:19]3[CH2:20][CH2:21][CH2:22][C:23](=O)[C:18]=3[O:17][N:16]=2)[CH:6]=[CH:7][C:8]=1[N:9]1[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]1.[F:25][C:26]1[CH:32]=[CH:31][C:29]([NH2:30])=[CH:28][CH:27]=1.C(O)C.[BH4-].[Na+]>C1COCC1>[F:25][C:26]1[CH:32]=[CH:31][C:29]([NH:30][CH:23]2[C:18]3[O:17][N:16]=[C:15]([C:5]4[CH:6]=[CH:7][C:8]([N:9]5[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]5)=[C:3]([O:2][CH3:1])[CH:4]=4)[C:19]=3[CH2:20][CH2:21][CH2:22]2)=[CH:28][CH:27]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 97314-FluoroanilineHCID 4311764Sodium borohydrideHCID 895451743-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-5,6-dihydrobenzo[d]isoxazol-7(4H)-one

Product 1

HCID 71552188HCID 71552188, compoundYield 60.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-5,6-dihydrobenzo[d]isoxazol-7(4H)-one (850 mg, 2.6 mmol) and 4-fluoroaniline (877 mg, 7.89 mmol) in THF (10 mL) was added Ti(OPr-i)4 (823 mg, 2.9 mmol) and the reaction mixture was stirred at 60° C. overnight. The mixture was cooled to 0° C., and 10.0 mL of dry ethanol was added, followed by NaBH4 (149 mg, 3.4 mmol). The mixture was stirred for 1 hr, precipitate was removed by filtration and washed with ethyl acetate. The filtrate was partitioned between water and ethyl acetate. The aqueous phase was extracted with ethyl acetate. The combined organic phase was washed with brine, dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography using a gradient of 0-7% of MeOH in DCM to afford the 660 mg of the title product.

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. stirringThe mixture was stirred for 1 hr
  3. customprecipitate was removed by filtration
  4. washwashed with ethyl acetate
  5. customThe filtrate was partitioned between water and ethyl acetate
  6. extractionThe aqueous phase was extracted with ethyl acetate
  7. washThe combined organic phase was washed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customThe crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-2cd16dfc7e7944d0ba64493a45c20f30
Source dataset
uspto-grants-2015_08
Patent number
US09096582B2

Reaction notes

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