Aluminium lithium hydride → (2R,5S)-1-(4-fluorobenzyl)-2-(hydroxy)methyl-5-methylpiperazine

HRID 489197Notes

Reaction equation

HRID 489197 reaction equation
[F:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][N:7]2[C:12](=O)[C@H:11]([CH3:14])[NH:10][C:9](=O)[C@H:8]2[CH2:16][OH:17])=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[F:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][N:7]2[CH2:12][C@H:11]([CH3:14])[NH:10][CH2:9][C@@H:8]2[CH2:16][OH:17])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 57116208(2R,5S)-1-(4-fluorobenzyl)-2-(hydroxy)methyl-5-methylpiperazine-3,6-dione

Product 1

HCID 57226061(2R,5S)-1-(4-fluorobenzyl)-2-(hydroxy)methyl-5-methylpiperazineYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of (2R,5S)-1-(4-fluorobenzyl)-2-(hydroxy)methyl-5-methylpiperazine-3,6-dione (2.0 g, 7.5 mmol) in anhydrous tetrahydrofuran (50 mL) under N2 at 0° C. was carefully added lithium aluminum hydride (2.2 g, 60 mmol). The resulting suspension was heated to reflux. After 15 hours, the mixture was cooled to ambient temperature and carefully quenched with water (2 mL), then 1 N aqueous KOH solution (6 mL). The resulting suspension was stirred at ambient temperature for 30 minutes, then filtered through Celite (ethyl acetate). The filtrate was concentrated in vacuo to afford 1.6 g (90% yield) of (2R,5S)-1-(4-fluorobenzyl)-2-(hydroxy)methyl-5-methylpiperazine, a compound of formula (S), as a white solid; NMR (CDCl3) 7.3 (dd, 2), 7.0 (dd, 2), 4.2-4.0 (m, 2), 3.5 (d, 1) 3.0 (m, 2), 2.7 (m, 2), 1.7 (m, 1), 1.0 (d, 3).

Workup

  1. temperatureThe resulting suspension was heated to reflux
  2. customcarefully quenched with water (2 mL)
  3. filtrationfiltered through Celite (ethyl acetate)
  4. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-7f2eaa78cb4e4fb0814d4d5fe12a4712
Source dataset
uspto-grants-2005_12
Patent number
US06977258B2

Reaction notes

Loading…