Phthalimide → N-[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]butyl]phthalimide

HRID 1420426Notes

Reaction equation

HRID 1420426 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[F:13][C:14]1[CH:33]=[CH:32][C:17]2[C:18]([CH:21]3[CH2:26][CH2:25][N:24]([CH:27]([CH2:30][CH3:31])[CH2:28]O)[CH2:23][CH2:22]3)=[N:19][O:20][C:16]=2[CH:15]=1.[C:34]1(=[O:44])[NH:38][C:37](=[O:39])[C:36]2=[CH:40][CH:41]=[CH:42][CH:43]=[C:35]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.CCOCC>[F:13][C:14]1[CH:33]=[CH:32][C:17]2[C:18]([CH:21]3[CH2:26][CH2:25][N:24]([CH:27]([CH2:30][CH3:31])[CH2:28][N:38]4[C:37](=[O:39])[C:36]5=[CH:40][CH:41]=[CH:42][CH:43]=[C:35]5[C:34]4=[O:44])[CH2:23][CH2:22]3)=[N:19][O:20][C:16]=2[CH:15]=1

Participants

7

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 18467277HCID 18467277, compound

Product 1

HCID 18467212N-[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]butyl]phthalimideYield 7.6%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of diethyl azodicarboxylate (DEAD, 4.9 g, 28.3 mmol) in THF (50 ml) was added dropwise to a solution of 2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]butanol (6.9 g, 23.6 mmol), phthalimide (4.16 g, 1.2 eq), and triphenylphosphine (7.4 g, 28.3 mmol) in THF (200 ml) at room temperature. The solution was stirred at room temperature for 24 hours. After the reaction, the solvent was stripped to dryness. The residue was stirred in ether (200 ml) and the insolubles were removed by filtration. The oily residue from concentration of the ether solution was purified by two flash chromatography (SiO2, 75 g, eluted with dichloromethane, DCM, and 1-2% CH3OH in DCM) and (100 g of SiO2 ; eluted with DCM, 11, and 1% CH3OH in DCM, 1.21). Two close compounds were separated and the top compound on TLC (1.6 g) was recrystallized from isopropyl ether to yield 0.76 g of white crystals, m.p. 86°-88° C.

Workup

  1. customAfter the reaction
  2. customthe insolubles were removed by filtration
  3. customThe oily residue from concentration of the ether solution was purified by two flash chromatography (SiO2, 75 g, eluted with dichloromethane, DCM, and 1-2% CH3OH in DCM) and (100 g of SiO2 ; eluted with DCM, 11, and 1% CH3OH in DCM, 1.21)
  4. customTwo close compounds
  5. customwere separated
  6. customthe top compound on TLC (1.6 g) was recrystallized from isopropyl ether

Sources & evidence

ORD record
ord-72e0dc0f66a2475ca3816b8a96b7b765
Source dataset
uspto-grants-1999_03
Patent number
US05889035

Reaction notes

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