Potassium Carbonate → N-[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethvl]-2,3-dihydro-5-(triisopropylsilyl)oxy-1H-isoindole difumarate

HRID 370240Notes

Reaction equation

HRID 370240 reaction equation
[F:1][C:2]1[CH:19]=[CH:18][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][NH2:17])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.Br[C:21]1([CH3:40])[CH:26]=[CH:25][C:24]([O:27][Si:28]([CH:35]([CH3:37])[CH3:36])([CH:32]([CH3:34])[CH3:33])[CH:29]([CH3:31])[CH3:30])=[CH:23][C:22]1(Br)[CH3:38].[C:41]([O-:44])([O-:43])=O.[K+].[K+]>C(#N)C>[C:4]([OH:27])(=[O:8])/[CH:5]=[CH:18]/[C:41]([OH:44])=[O:43].[C:24]([OH:27])(=[O:8])/[CH:25]=[CH:26]/[C:41]([OH:44])=[O:43].[F:1][C:2]1[CH:19]=[CH:18][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][N:17]4[CH2:38][C:22]5[C:21](=[CH:26][CH:25]=[C:24]([O:27][Si:28]([CH:32]([CH3:34])[CH3:33])([CH:29]([CH3:31])[CH3:30])[CH:35]([CH3:36])[CH3:37])[CH:23]=5)[CH2:40]4)[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 146998572-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)ethan-1-amineHCID 670710041,2-Dibromo-4-(triisopropyisilyl)oxy-xylene

Product 1

HCID 67071185N-[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethvl]-2,3-dihydro-5-(triisopropylsilyl)oxy-1H-isoindole difumarate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethylamine (1.52 g, 5.73 mmol), 1,2-dibromo-4-(triisopropylsilyl)oxy-xylene (2.4 g, 5.7 mmol) and K2CO3 (1.8 g, 13 mmol) in acetonitrile (300 ml) was stirred overnight (18 hours) at room temperature. The mixture was filtered and the solvent was stripped. The residue was purified by flash chromatography over a silica gel column (7 gm of SiO2 ; eluted with 1-3% CH3OH in dichloromethane. The product thus purified (weight: 900 mg) was converted to the fumarate salt by treatment with fumaric acid (194 mg) in hot ethanol. The crystals were collected and weighed 590 mg, m.p. 208-210° C.

Workup

  1. filtrationThe mixture was filtered
  2. customThe residue was purified by flash chromatography over a silica gel column (7 gm of SiO2
  3. washeluted with 1-3% CH3OH in dichloromethane
  4. customThe product thus purified (weight: 900 mg)
  5. customThe crystals were collected

Sources & evidence

ORD record
ord-28ae88ec73f147aa9db40c25655da850
Source dataset
uspto-grants-2000_10
Patent number
US06140345

Reaction notes

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