Aluminium lithium hydride → (S)-2-(4-benzylpiperazin-2-yl)ethanol

HRID 131394Notes

Reaction equation

HRID 131394 reaction equation
C[O:2][C:3](=O)[CH2:4][C@H:5]1[C:10](=O)[N:9]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:8][C:7](=O)[NH:6]1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[CH2:12]([N:9]1[CH2:8][CH2:7][NH:6][C@@H:5]([CH2:4][CH2:3][OH:2])[CH2:10]1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 59732116612506-99-7

Product 1

HCID 23395653(S)-2-(4-benzylpiperazin-2-yl)ethanolYield 100.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a 0° C. solution of (S)-(4-benzyl-3,6-dioxopiperazin-2-yl)acetic acid methyl ester (31.9 g, 0.12 mol) in tetrahydrofuran (1 L), add lithium aluminum hydride via slow cannulation (350 mL of a commercial 1.0 M solution in tetrahydrofuran). Stir at room temperature overnight, quench by successive careful addition of 13.3 mL of water, 13.3 mL of 15% aqueous sodium hydroxyde, and 39.9 mL of water, all the while with vigourous stirring to ensure formation of a fine precipitate. Filter through a fritted funnel, washing the solids well with tetrahydrofuran and dichloromethane. Concentrate in vacuo to provide 26.5 g of an oily residue, apply directly to a silica gel column. Elute with a 5% mixture of 7N ammonia-methanol in dichloromethane, to obtain the desired product as an orange oil which solidifies under vacuum. Take up the solid in acetonitrile and sonicate for a few minutes. Filter the resulting precipitate to obtain 7.5 g (25%) of the title compound as an off-white crystalline solid, mp 78.9-80.4° C. Concentrate the mother liquor to obtain 6.8 g (23%) of slightly less pure material as an amorphous solid: mass spectrum (ES): m/e 221.3 (M+1); specific Rotation: −7.84.

Workup

  1. customquench by successive careful addition of 13.3 mL of water, 13.3 mL of 15% aqueous sodium hydroxyde, and 39.9 mL of water, all the while
  2. stirringwith vigourous stirring
  3. filtrationFilter through a fritted funnel
  4. washwashing the solids well with tetrahydrofuran and dichloromethane
  5. concentrationConcentrate in vacuo

Sources & evidence

ORD record
ord-cd0a0db144ee4be8bb78b58243353fe5
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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