Sodium Iodide → HCID 19786559, compound

HRID 1196583Notes

Reaction equation

HRID 1196583 reaction equation
Cl[CH2:2][CH2:3][CH2:4][CH:5]1[C:19](=[O:20])[C:9]2[C:10]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[N:11][O:12][C:8]=2[CH2:7][CH2:6]1.C(N(C(C)C)CC)(C)C.[Cl:30][C:31]1[CH:36]=[CH:35][C:34]([C:37]2([OH:43])[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]2)=[CH:33][CH:32]=1.[I-].[Na+]>CN(C=O)C>[Cl:30][C:31]1[CH:36]=[CH:35][C:34]([C:37]2([OH:43])[CH2:38][CH2:39][N:40]([CH2:2][CH2:3][CH2:4][CH:5]3[C:19](=[O:20])[C:9]4[C:10]([C:13]5[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=5)=[N:11][O:12][C:8]=4[CH2:7][CH2:6]3)[CH2:41][CH2:42]2)=[CH:33][CH:32]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 382824-(4-Chlorophenyl)-4-hydroxypiperidineHCID 81531DiisopropylethylamineHCID 19786584HCID 19786584, compound

Product 1

HCID 19786559HCID 19786559, compoundYield 32.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution consisting of 5-(3-chloropropyl)-6,7-dihydro-3-phenyl-1,2-benzisoxazol-4(5H)-one (5.02 g) and DMF (170 ml) was added diisopropylethyl amine (7.50 ml), 4-(4-chlorophenyl)-4-hydroxypiperidine (4.03 g) and sodium iodide (2.59 g) at room temperature with stirring. The reaction was flushed with nitrogen and warmed to 78°-80° C. for 11 hours. Upon cooling to room temperature, water and ethyl acetate were added to the reaction mixture. The layers were separated and the aqueous layers extracted three times with ethyl acetate. The combined organic layers were washed with brine and dried (MgSO4). Filtration and concentration gave the crude amine product. Purification via flash chromatography (silica gel, 2% Et3N/ether) afforded 2.60 g of the desired product as an oil. Addition of ether, heat, and slow evaporation gave a powder. The ether was then decanted and the powder was washed with pentane to yield 5-[3-(4-(4-chlorophenyl)-4-hydroxy-piperidinyl)-propyl]-6,7-dihydro-3-phenyl-1,2-benzisoxazol- 4(5H)-one, m.p. 147°-148° C.

Workup

  1. customThe reaction was flushed with nitrogen
  2. temperaturewarmed to 78°-80° C. for 11 hours
  3. additionwater and ethyl acetate were added to the reaction mixture
  4. customThe layers were separated
  5. extractionthe aqueous layers extracted three times with ethyl acetate
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationFiltration and concentration
  9. customgave the crude amine product
  10. customPurification via flash chromatography (silica gel, 2% Et3N/ether)

Sources & evidence

ORD record
ord-7131c539da104a638e6be96fa177b064
Source dataset
uspto-grants-1992_05
Patent number
US05114936

Reaction notes

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