Water → HCID 19786560, compound

HRID 1657096Notes

Reaction equation

HRID 1657096 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:12]2[C:13](=[O:17])[CH2:14][CH2:15][CH2:16][C:11]=2[O:10][N:9]=1.C([N-]C(C)C)(C)C.[Li+].[Cl:26][CH2:27][CH2:28][CH2:29]I.O>C1COCC1.CCCCCC.ClCCl.CCOCC>[Cl:26][CH2:27][CH2:28][CH2:29][CH:14]1[C:13](=[O:17])[C:12]2[C:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[F:1])=[N:9][O:10][C:11]=2[CH2:16][CH2:15]1

Participants

9

Reactant 4

HCID 962WaterHCID 813631-Chloro-3-iodopropaneHCID 2724682Lithium diisopropylamideHCID 19786555HCID 19786555, compound

Product 1

HCID 19786560HCID 19786560, compound

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

In 500 ml anhydrous THF was dissolved 15.0 g 6,7-dihydro-3-(2-fluorophenyl) -1,2-benzisoxazol-4(5H)-one under nitrogen atmosphere with stirring. The solution was cooled to -78° C. and 65.0 ml lithium diisopropylamide (1.5 molar in cyclohexane) was added dropwise. The resulting solution was stirred for ten minutes at -78° C. and 9.10 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 three 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 with 10% dichloromethane in hexane and gradually increase polarity to 100% dichloromethane) gave 5.30 g of 5-(3-chloropropyl)-6,7-dihydro-3-(2-fluorophenyl)-1,2-benzisoxazol-4(5H)-one as an oil.

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 three 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

Sources & evidence

ORD record
ord-bef4682bcdf64ca086185a55929c30ee
Source dataset
uspto-grants-1993_10
Patent number
US05256672

Reaction notes

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