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

HRID 1459822Notes

Reaction equation

HRID 1459822 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 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-9bd3692deeec4ed999417e2258565459
Source dataset
uspto-grants-1998_12
Patent number
US05854243

Reaction notes

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