Potassium Carbonate → 6-Fluoro-3-[1-[3-(2-methoxyphenoxy)propyl]-4-piperidinyl]-1,2-benzisoxazole fumarate

HRID 1899461Notes

Reaction equation

HRID 1899461 reaction equation
[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.C([O-])([O-])=O.[K+].[K+].[CH3:23][O:24][C:25]1[CH:35]=[CH:34][CH:33]=[CH:32][C:26]=1[O:27][CH2:28][CH2:29][CH2:30]Cl.[C:36]([OH:43])(=[O:42])/[CH:37]=[CH:38]/[C:39]([OH:41])=[O:40]>C(#N)C.C(O)C>[C:36]([OH:43])(=[O:42])/[CH:37]=[CH:38]/[C:39]([OH:41])=[O:40].[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([CH2:30][CH2:29][CH2:28][O:27][C:26]4[CH:32]=[CH:33][CH:34]=[CH:35][C:25]=4[O:24][CH3:23])[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 444972Fumaric AcidHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazoleHCID 147153523-(2-Methoxyphenoxy)propyl chloride

Product 1

HCID 219600506-Fluoro-3-[1-[3-(2-methoxyphenoxy)propyl]-4-piperidinyl]-1,2-benzisoxazole fumarate

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2.45 g; 11.1 mmol), K2CO3 (2.0 g), and 3-(2-methoxyphenoxy)propyl chloride (3.5 g, 17.4 mmol) in acetonitrile (40 ml) was heated at 90° C. for 4 hours. At the end of the reaction, the solvent was removed, and the solids were dissolved into dichloromethane (100 ml). The solution was washed with water and brine, then dried over MgSO4. The crude material from the solution was combined with 1.2 g of crude material prepared in the same fashion (using 0.5 g of starting material). The combined material was purified by flash chromatography on a silica gel column (49 g, eluted with 0.5% diethylamine: 1% methanol:98.5% dichloromethane, 1 L). The fractions containing the pure product were pooled and concentrated down to a light oil (3.68 g). This oil was treated with fumaric acid (1.14 g, 9.8 mmol) in ethanol (13 ml). The 6-fluoro-3-[1-[3-(2-methoxyphenoxy)-propyl]-4-piperidinyl]-1,2-benzisoxazole fumarate crystals obtained weighed 4.01 g (60%), m.p.=169°-170° C.

Workup

  1. customAt the end of the reaction
  2. customthe solvent was removed
  3. dissolutionthe solids were dissolved into dichloromethane (100 ml)
  4. washThe solution was washed with water and brine
  5. dry with materialdried over MgSO4
  6. customprepared in the same fashion (using 0.5 g of starting material)
  7. customThe combined material was purified by flash chromatography on a silica gel column (49 g, eluted with 0.5% diethylamine: 1% methanol:98.5% dichloromethane, 1 L)
  8. additionThe fractions containing the pure product
  9. concentrationconcentrated down to a light oil (3.68 g)

Sources & evidence

ORD record
ord-f8ec7e994c364095b1f0f677bd696ed8
Source dataset
uspto-grants-1996_11
Patent number
US05571828

Reaction notes

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