N-[(4-fluorophenyl)methylidene]hydroxylamine → 5-(3-chloropropyl)-6,7-dihydro-3-(4-fluorophenyl)-1,2-benzisoxazol-4(5H)-one

HRID 1196586Notes

Reaction equation

HRID 1196586 reaction equation
FC1C=CC(C=NO)=CC=1.[F:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[C:22]3[C:23](=[O:27])[CH2:24][CH2:25][CH2:26][C:21]=3[O:20][N:19]=2)=[CH:14][CH:13]=1.C([N-]C(C)C)(C)C.[Li+].[Cl:36][CH2:37][CH2:38][CH2:39]I>C1COCC1.O>[Cl:36][CH2:37][CH2:38][CH2:39][CH:24]1[C:23](=[O:27])[C:22]2[C:18]([C:15]3[CH:14]=[CH:13][C:12]([F:11])=[CH:17][CH:16]=3)=[N:19][O:20][C:21]=2[CH2:26][CH2:25]1

Participants

7

Reactant 4

HCID 68017N-[(4-fluorophenyl)methylidene]hydroxylamineHCID 813631-Chloro-3-iodopropaneHCID 2724682Lithium diisopropylamideHCID 197865586,7-dihydro-3-(4-fluorophenyl)-1,2-benzisoxazol-4(5H)-one

Product 1

HCID 197865615-(3-chloropropyl)-6,7-dihydro-3-(4-fluorophenyl)-1,2-benzisoxazol-4(5H)-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

In a similar manner to that of Examples 7a-d starting with 4-fluorobenzaldehyde oxime, the starting ketone is prepared. In 170 ml anhydrous THF was dissolved 4.0 g 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 17.3 ml lithium diisopropylamide (1.50 molar in cyclohexane) was added dropwise. The resulting solution was stirred for ten minutes at -78° C. and 2.2 ml 1-chloro-3-iodopropane was added. Upon warming to room temperature, the reaction mixture was poured into water and the layers were then separated. The aqueous phase was extracted twice with dichloromethane and once with ether. The combined organic layers were washed with brine and dried (MgSO4). Filtration and concentration gave the crude product. Column chromatography on silica gel (start with 10% dichloromethane in hexane and gradually increase polarity to 100% dichloromethane) gave 4.2 g of 5-(3-chloropropyl)-6,7-dihydro-3-(4-fluorophenyl)-1,2-benzisoxazol-4(5H)-one.

Workup

  1. stirringThe resulting solution was stirred for ten minutes at -78° C.
  2. temperatureUpon warming to room temperature
  3. customthe layers were then separated
  4. extractionThe aqueous phase was extracted twice with dichloromethane and once with ether
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationFiltration and concentration
  8. customgave the crude product

Sources & evidence

ORD record
ord-ee1af6f93f3b42fb977a0083d8d2b521
Source dataset
uspto-grants-1992_05
Patent number
US05114936

Reaction notes

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