Potassium Carbonate → 4-(6-Fluoro-1,2-benzisoxazol-yl)-1-[3-(2,3-dihydro-1H-isoindol-2-yl)propyl]piperidine Difumarate

HRID 2270017Notes

Reaction equation

HRID 2270017 reaction equation
[F:1][C:2]1[CH:20]=[CH:19][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][NH2:18])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH:28](Br)[C:29]1[C:30]([CH3:35])=[CH:31][CH:32]=[CH:33][CH:34]=1.[C:37]([OH:44])(=[O:43])/[CH:38]=[CH:39]/[C:40]([OH:42])=[O:41]>C(#N)C.C(O)C>[C:37]([OH:44])(=[O:43])/[CH:38]=[CH:39]/[C:40]([OH:42])=[O:41].[C:37]([OH:44])(=[O:43])/[CH:38]=[CH:39]/[C:40]([OH:42])=[O:41].[F:1][C:2]1[CH:20]=[CH:19][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][N:18]4[CH2:35][C:30]5[C:29](=[CH:34][CH:33]=[CH:32][CH:31]=5)[CH2:28]4)[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 444972Fumaric AcidHCID 6390401-(Dibromomethyl)-2-methylbenzeneHCID 146998441-(Aminopropyl)-4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine

Product 1

HCID 670711894-(6-Fluoro-1,2-benzisoxazol-yl)-1-[3-(2,3-dihydro-1H-isoindol-2-yl)propyl]piperidine Difumarate

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 6342AcetonitrileSolvent

Procedure

A stirred mixture of 3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propyl amine (3.46 g, 12.5 mmol), K2CO3 (4 g, 29 mmol) and α,α-dibromo-o-xylene (3.3 g, 12.5 mmol) in acetonitrile (300 ml) was heated at reflux for 3.5 hours. The mixture was cooled and the insolubles were filtered. The mixture was cooled and concentrated down to a dark oil. The oil was purified by flash chromatography over a silica gel column (SiO2, 45 g; eluted with dichloromethane and MeOH in dichloromethane). The product thus obtained weighed 1.95 g as an oil. This oil was dissolved in ethanol and was treated with a solution of fumaric acid (600 mg) in ethanol. The resulting crystals were collected as an off white solid and weighed 1.44 gm, m.p. 206°-209° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 3.5 hours
  3. temperatureThe mixture was cooled
  4. filtrationthe insolubles were filtered
  5. temperatureThe mixture was cooled
  6. concentrationconcentrated down to a dark oil
  7. customThe oil was purified by flash chromatography over a silica gel column (SiO2, 45 g; eluted with dichloromethane and MeOH in dichloromethane)
  8. customThe product thus obtained
  9. customThe resulting crystals were collected as an off white solid

Sources & evidence

ORD record
ord-87815b56ac6b43ae99b77d12d6e83ae1
Source dataset
uspto-grants-2001_12
Patent number
USRE037478E1

Reaction notes

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