Diisopropylethylamine → HCID 19786594, compound

HRID 1657106Notes

Reaction equation

HRID 1657106 reaction equation
[C:1]1([C:7]2[C:11]3[CH:12]([OH:29])[CH:13]([CH2:16][CH2:17]OS(C4C=CC(C)=CC=4)(=O)=O)[CH2:14][CH2:15][C:10]=3[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(C(C)C)CC)(C)C.Cl.[F:40][C:41]1[CH:54]=[CH:53][C:44]([C:45]([CH:47]2[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]2)=[O:46])=[CH:43][CH:42]=1>CN(C=O)C>[F:40][C:41]1[CH:42]=[CH:43][C:44]([C:45]([CH:47]2[CH2:52][CH2:51][N:50]([CH2:17][CH2:16][CH:13]3[CH:12]([OH:29])[C:11]4[C:7]([C:1]5[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=5)=[N:8][O:9][C:10]=4[CH2:15][CH2:14]3)[CH2:49][CH2:48]2)=[O:46])=[CH:53][CH:54]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 3084438p-Fluorophenyl 4-piperidyl ketone hydrochlorideHCID 19786608HCID 19786608, compound

Product 1

HCID 19786594HCID 19786594, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution consisting of 3-phenyl-5-(2-tosyloxyethyl)-4-hydroxy-4,5,6,7-tetrahydro-1,2-benzisoxazole (8.0 g) and DMF (100 n-il) was added diisopropylethyl amine (6.7 ml) and 4-(4-fluorobenzoyl)piperidine hydrochloride (7.1 g) at room temperature with stirring. The flask was flushed with nitrogen and warmed to 80° C. for 4.5 hours. Upon cooling to room temperature, water and ethyl acetate were added to the reaction mixture. The layers were separated and the aqueous phase was extracted 3 times with ethyl acetate. The combined organic layers were washed with brine and dried (MgSO4). Filtration and concentration gave the crude product. Purification via flash column chromatography (silica gel, 2% triethylamine/ether) afforded 1.3 g of 5-[2-(4-(4-fluorobenzoyl)-1-piperidinyl)-ethyl]-3-phenyl-4-hydroxy-4,5,6,7-tetrahydro-1,2-benzisoxazole.

Workup

  1. customThe flask was flushed with nitrogen
  2. temperatureUpon cooling to room temperature
  3. additionwater and ethyl acetate were added to the reaction mixture
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted 3 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 product
  10. customPurification via flash column chromatography (silica gel, 2% triethylamine/ether)

Sources & evidence

ORD record
ord-02ec96d1e407462aada61faa06c45eb8
Source dataset
uspto-grants-1993_10
Patent number
US05256672

Reaction notes

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