Water → 5-(3-chloropropyl)-6,7-dihydro-3-(4-fluorophenyl)-7-methyl-1,2-benzisoxazol-4(5H)-one

HRID 1657101Notes

Reaction equation

HRID 1657101 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][CH:5]1[C:20](=[O:21])[C:9]2[C:10]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)=[N:11][O:12][C:8]=2[CH2:7][CH2:6]1.[CH:22]([N-]C(C)C)(C)C.[Li+].IC.O>C1COCC1.CCOCC>[Cl:1][CH2:2][CH2:3][CH2:4][CH:5]1[C:20](=[O:21])[C:9]2[C:10]([C:13]3[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=3)=[N:11][O:12][C:8]=2[CH:7]([CH3:22])[CH2:6]1

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 197865615-(3-chloropropyl)-6,7-dihydro-3-(4-fluorophenyl)-1,2-benzisoxazol-4(5H)-one

Product 1

HCID 197865565-(3-chloropropyl)-6,7-dihydro-3-(4-fluorophenyl)-7-methyl-1,2-benzisoxazol-4(5H)-one

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

In 140 ml anhydrous THF was dissolved 4.20 g 5-(3-chloropropyl)-6,7-dihydro-3-(4-fluorophenyl)-1,2-benzisoxazol-4(5H)-one under nitrogen atmosphere, with stirring. The solution was cooled to -78° C. and 14.0 ml lithium diisopropylamide (1.5 molar in cyclohexane) was added dropwise. The resulting solution was stirred for 10 minutes at -78° C. and 1.30 ml iodomethane was added. Upon warming to room temperature, the reaction mixture was poured into water and ether. The layers were separated and the aqueous phase was extracted two times with dichloromethane and once with ether. The combined organic layers were washed with brine and dried (MgSO4). Filtration and concentration gave the crude product as an oil. Column chromatography on silica gel (start eluting with 10% dichloromethane in hexane and gradually increase polarity to 100% dichloromethane) afforded 4.00 g of 5-(3-chloropropyl)-6,7-dihydro-3-(4-fluorophenyl)-7-methyl-1,2-benzisoxazol-4(5H)-one as an oil.

Workup

  1. stirringThe resulting solution was stirred for 10 minutes at -78° C.
  2. temperatureUpon warming to room temperature
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted two times with dichloromethane
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationFiltration and concentration
  8. customgave the crude product as an oil
  9. washColumn chromatography on silica gel (start eluting with 10% dichloromethane in hexane and gradually increase polarity to 100% dichloromethane)

Sources & evidence

ORD record
ord-f871ee3a248044ae86d7a926352aa64b
Source dataset
uspto-grants-1993_10
Patent number
US05256672

Reaction notes

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