Aluminium lithium hydride → [2-Methoxy-4-[(4-methylpiperazin-1-yl)methyl]phenyl]methanol

HRID 632506Notes

Reaction equation

HRID 632506 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].C[O:8][C:9](=O)[C:10]1[CH:15]=[CH:14][C:13]([CH2:16][N:17]2[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]2)=[CH:12][C:11]=1[O:24][CH3:25].[OH-].[Na+].O>C1COCC1>[CH3:25][O:24][C:11]1[CH:12]=[C:13]([CH2:16][N:17]2[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]2)[CH:14]=[CH:15][C:10]=1[CH2:9][OH:8]

Participants

5

Reactant 3

HCID 21226445Aluminium lithium hydrideHCID 23719242Sodium hydroxide--water (1/1/1)HCID 1178889242-Methoxy-4-[(4-methylpiperazin-1-yl)methyl]benzoic acid methyl ester

Product 1

HCID 117888927[2-Methoxy-4-[(4-methylpiperazin-1-yl)methyl]phenyl]methanolYield 98%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To 200 mL of a suspension of 5.21 g of LAH in THF cooled with ice was added dropwise, under argon flow, 50 mL of a solution of 25.5 g of 2-methoxy-4-[(4-methylpiperazin-1-yl)methyl]benzoic acid methyl ester in THF. The mixture was stirred under ice cooling for 1 hour and further stirred at room temperature for 22 hours. To the reaction mixture cooled with ice, 25 mL of a 10% NaOH water was added dropwise. After 30-minute stirring, the mixture was filtered through Celite. The filtrate was washed with 150 mL of THF and then was concentrated. To the residue, 50 mL of saturated brine and 300 mL of dichloromethane were added, and the organic layer was separated. The organic layer was concentrated. The residue was purified by silica gel column chromatography (CHCl3/methanol system) to give 22.4 g of the title compound (98% yield).

Workup

  1. stirringfurther stirred at room temperature for 22 hours
  2. additionwas added dropwise
  3. stirringAfter 30-minute stirring
  4. filtrationthe mixture was filtered through Celite
  5. washThe filtrate was washed with 150 mL of THF
  6. concentrationwas concentrated
  7. additionTo the residue, 50 mL of saturated brine and 300 mL of dichloromethane were added
  8. customthe organic layer was separated
  9. concentrationThe organic layer was concentrated
  10. customThe residue was purified by silica gel column chromatography (CHCl3/methanol system)

Sources & evidence

ORD record
ord-04488aed2d044dcdaf1965157cbf9984
Source dataset
uspto-grants-2016_04
Patent number
US09321752B2

Reaction notes

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