1-Chloro-3-iodopropane → 5-(3-Chloropropyl)-6,7-dihydro-3-(3-fluorophenyl)-1,2-benzisoxazol-4(5H)-one

HRID 1657100Notes

Reaction equation

HRID 1657100 reaction equation
FC1C=C(C=CC=1)C=NO.[F:11][C:12]1[CH:13]=[C:14]([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:15]=[CH:16][CH:17]=1.C([N-]C(C)C)(C)C.[Li+].[Cl:36][CH2:37][CH2:38][CH2:39]I>C1COCC1.CCOCC.O>[Cl:36][CH2:37][CH2:38][CH2:39][CH:24]1[C:23](=[O:27])[C:22]2[C:18]([C:14]3[CH:15]=[CH:16][CH:17]=[C:12]([F:11])[CH:13]=3)=[N:19][O:20][C:21]=2[CH2:26][CH2:25]1

Participants

8

Reactant 4

HCID 813631-Chloro-3-iodopropaneHCID 18088153-Fluorobenzaldehyde oximeHCID 2724682Lithium diisopropylamideHCID 197865546,7-dihydro-3-(3-fluorophenyl)-1,2-benzisoxazol-4(5H)-one

Product 1

HCID 197865475-(3-Chloropropyl)-6,7-dihydro-3-(3-fluorophenyl)-1,2-benzisoxazol-4(5H)-one

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

In a similar manner to that of Examples 7a-d starting with 3-fluorobenzaldehyde oxime, the starting ketone is prepared. In 200 ml anhydrous THF was dissolved 11.4 g 6,7-dihydro-3-(3-fluorophenyl)-1,2-benzisoxazol-4(5H)-one under nitrogen atmosphere with stirring. The solution was cooled to -78° C. and 49.4 ml lithium diisopropylamide (1.5 molar in cyclohexane) was added dropwise. The resulting solution was stirred for ten minutes at -78° C. and 6.4 ml 1-chloro-3-iodopropane 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 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 4.5 g of 5-(3-chloropropyl)-6,7-dihydro-3-(3-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 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-9d58ab58b8674d5c94b5b81af1b05d87
Source dataset
uspto-grants-1993_10
Patent number
US05256672

Reaction notes

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