Ethyl Acetate → 4-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]2-methyl-2-hydroxybutane fumarate

HRID 864193Notes

Reaction equation

HRID 864193 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][C:17]([O:19]CC)=[O:18])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.[CH3:24][Mg]Br.[NH4+].[Cl-].CC[O:31][C:32]([CH3:34])=[O:33]>O1CCCC1>[C:32]([OH:33])(=[O:31])/[CH:15]=[CH:16]/[C:17]([OH:19])=[O:18].[F:1][C:2]1[CH:23]=[CH:22][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][C:32]([CH3:34])([OH:33])[CH3:24])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 21959991Ethyl 3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)1-piperidinyl]propionateHCID 178418573HCID 178418573, compound

Product 1

HCID 219601024-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]2-methyl-2-hydroxybutane fumarate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of ethyl 3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propionate (3.21 g, 10 mmol) in tetrahydrofuran (THF, 100 ml), was added methylmagnesium bromide (10 ml, 30 mmol, 3M solution in ether) dropwise over 15 minutes at room temperature under N2. The resulting mixture was stirred for 16 hours. The mixture was slowly hydrolyzed with aqueous NH4Cl solution. The THF solution was diluted with EtOAc (300 ml), then was washed with water and brine. The organic solution was separated and dried over MgSO4. After removal of solvent, the crude product was purified by flash chromatography (25 g, SiO2, eluted with 1 CH3OH:99 DCM). The material thus purified weighed 2.36 g (77%) as white crystals. This was converted to the fumarate salt by treatment with fumaric acid (895 mg) in ethanol. Recrystallization from ethanol yielded white crystals, 2.47 g, m.p.=156°-158° C.

Workup

  1. washwas washed with water and brine
  2. customThe organic solution was separated
  3. dry with materialdried over MgSO4
  4. customAfter removal of solvent
  5. customthe crude product was purified by flash chromatography (25 g, SiO2, eluted with 1 CH3OH:99 DCM)
  6. customThe material thus purified
  7. customRecrystallization from ethanol yielded white crystals, 2.47 g, m.p.=156°-158° C.

Sources & evidence

ORD record
ord-4df8b100bbee4339a663d7ed58952144
Source dataset
uspto-grants-1996_10
Patent number
US05561128

Reaction notes

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