Potassium Carbonate → 3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)1-piperidinyl]-2,2-dimethyl1-propanol fumarate

HRID 2379987Notes

Reaction equation

HRID 2379987 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:17]([O-:20])([O-:19])=O.[K+].[K+].Br[CH2:24][C:25]([CH3:29])([CH3:28])[CH2:26][OH:27]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.O.C(#N)C>[C:4]([OH:27])(=[O:8])/[CH:5]=[CH:15]/[C:17]([OH:20])=[O:19].[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([CH2:24][C:25]([CH3:29])([CH3:28])[CH2:26][OH:27])[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 1425013-Bromo-2,2-dimethyl-1-propanolHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazole

Product 1

HCID 219600703-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)1-piperidinyl]-2,2-dimethyl1-propanol fumarate

Reagents, catalysts & solvents 3

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (3.0 gm, 13.6 mmoles), K2CO3 (12.5 gm, 17.5 mmoles), 3-bromo-2,2-dimethyl-1-propanol (3 gm, 21 mmoles, 1.5 eq.), tetrabutylammonium hydrogen sulfate (1 gm, phase transfer catalyst) in water (5 ml) and acetonitrile (150 ml) was heated at reflux for 43 days. TLC showed a small spot for the expected product. The mixture was diluted with EtOAc (400 ml) and washed with brine. The organic solution was dried and concentrated to a dark brown mixture. The crude mixture was purified carefully by flash chromatography (SiO2, 95 gm to afford the dried pure product; 260 mg, (6%) as an oil. This oil was converted to the fumarate salt by treatment with fumaric acid (98.5 mg, 1.0 eq.) in ethanol. Recrystallization from ethanol:ether yielded 210 mg of white crystals, m.p.=144°-145° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 43 days

Sources & evidence

ORD record
ord-560f68d190ae48768759aad5936bd940
Source dataset
uspto-grants-1994_11
Patent number
US05364866

Reaction notes

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