Sodium hydride → HCID 10622766, compound

HRID 2399375Notes

Reaction equation

HRID 2399375 reaction equation
[H-].[Na+].[NH:3]1[C:8](=[O:9])[CH2:7][CH2:6][CH2:5][C:4]1=[O:10].[CH3:11][CH:12]([O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[N:21]1[CH2:26][CH2:25][N:24]([CH2:27][C:28]2[CH:29]=[C:30]([CH:33]=[CH:34][CH:35]=2)[CH2:31]Cl)[CH2:23][CH2:22]1)[CH3:13]>CN(C=O)C>[CH3:13][CH:12]([O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[N:21]1[CH2:26][CH2:25][N:24]([CH2:27][C:28]2[CH:29]=[C:30]([CH2:31][N:3]3[C:8](=[O:9])[CH2:7][CH2:6][CH2:5][C:4]3=[O:10])[CH:33]=[CH:34][CH:35]=2)[CH2:23][CH2:22]1)[CH3:11]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 70726GlutarimideHCID 10406132HCID 10406132, compound

Product 1

HCID 10622766HCID 10622766, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A mixture of NaH (0.224g, 7.48 mmol) and DMF (10 mL) was treated slowly with 2,6-piperidinedione (0.846 g, 7.48 mmol) at room temperature. After the addition was complete, the mixture was cooled to 0° C. and a solution of 3-[3-[[1-[2-(1-methylethoxy)phenyl]-4-piperazinyl]methyl]benzyl chloride (2.46 g, 7.12 mmol) and DMF (10 mL) was added dropwise. The cooling bath was removed and the reaction was stirred at room temperature overnight. A small portion of water was added and the reaction was concentrated under vacuum. The residue was partitioned between CH2Cl2 /water and the organic layer was separated, dried, and evaporated to give 1-[[3-[[1-[2-(1-methylethoxy)phenyl]-4-piperazinyl]methyl]phenyl]methyl]-piperidine-2,6-dione as an oil, 3.25 g. This material was dissolved in i-PrOH (13 mL) and treated with maleic acid (0.83 g, 7.15 mmol). Trituration with ether, filtration, and drying afforded 1-[[3-[[1-[2-(1-methylethoxy)phenyl]-4-piperazinyl]methyl]phenyl]methyl]-piperidine-2,6-dione (Z)-2-butenedioate (1:1) as a white solid (2.73 g, 70%), m.p. 103°-105° C. 1H NMR and mass spectral analysis supported the assigned structure.

Workup

  1. additionAfter the addition
  2. customThe cooling bath was removed
  3. additionA small portion of water was added
  4. concentrationthe reaction was concentrated under vacuum
  5. customThe residue was partitioned between CH2Cl2 /water
  6. customthe organic layer was separated
  7. customdried
  8. customevaporated

Sources & evidence

ORD record
ord-34981be85a4949d0889f6691871d299b
Source dataset
uspto-grants-1995_09
Patent number
US05449677

Reaction notes

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