Water → N-[2-hydroxy-1-(4-methyl-piperazin-1-ylmethyl)ethyl]acetamide

HRID 1765452Notes

Reaction equation

HRID 1765452 reaction equation
[C:1]([NH:4][CH:5]([CH2:10][N:11]1[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]1)[C:6](OC)=[O:7])(=[O:3])[CH3:2].[BH4-].[Na+].O.ClCCl>CO>[OH:7][CH2:6][CH:5]([NH:4][C:1](=[O:3])[CH3:2])[CH2:10][N:11]1[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]1

Participants

6

Reactant 4

HCID 962WaterHCID 6344DichloromethaneHCID 4311764Sodium borohydride2×HCID 9964799Methyl 2-(acetylamino)-3-(4-methyl-piperazinyl)propanoate

Product 1

HCID 9899259N-[2-hydroxy-1-(4-methyl-piperazin-1-ylmethyl)ethyl]acetamideYield 31.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
20 °C

Procedure

A solution under inert atmosphere of 3.27 g of methyl (acetylamino)-3-(4-methyl-piperazin-1-yl)propanoate in 100 mL of anhydrous methanol is cooled at a temperature of about 10° C., then 0.76 g of sodium borohydride are added using a spatula. The reaction medium is stirred for 5 hours at a temperature of about 20° C., then are added again 0.26 g of sodium borohydride and the stirring is carried out for 38 hours. Then, 5 mL of water is dropped into the reaction mass which is heated and concentated under reduced pressure (2 kPa) at a temperature of about 30° C. The obtained residue is taken up with dichloromethane and the insoluble matter is removed by filtration. The filtrate is concentrated under reduced pressure (2 kPa) at a temperature of about 20° C. The residue is purified by chromatography under argon pressure (60 kPa), on a column of silica gel (particle size 40–63 μm; diameter 5 cm; height 19 cm), eluting with successive mixtures of 20% dichloromethane/methanol/aqueous ammonia (98/2/0, 95/5/0.1, 90/10/0.2, 80/20/0.25, 50/50/0.25 by volume). The fractions containing the expected product are combined and concentrated under reduced pressure (2 kPa) at a temperature of about 40° C. About 0.92 g of N-[2-hydroxy-1-(4-methyl-piperazin-1-ylmethyl)ethyl]acetamide are obtained in the form of a yellow-colored liquid. [Infrared spectrum CH2Cl2 3621; 3429; 3352; 2944; 2803; 1657; 1513; 1460; 1284; 1050; 1011 and 816 cm−1].

Workup

  1. waitthe stirring is carried out for 38 hours
  2. temperatureis heated
  3. customconcentated under reduced pressure (2 kPa) at a temperature of about 30° C
  4. customthe insoluble matter is removed by filtration
  5. concentrationThe filtrate is concentrated under reduced pressure (2 kPa) at a temperature of about 20° C
  6. customThe residue is purified by chromatography under argon pressure (60 kPa)
  7. washon a column of silica gel (particle size 40–63 μm; diameter 5 cm; height 19 cm), eluting with successive mixtures of 20% dichloromethane/methanol/aqueous ammonia (98/2/0, 95/5/0.1, 90/10/0.2, 80/20/0.25, 50/50/0.25 by volume)
  8. additionThe fractions containing the expected product
  9. concentrationconcentrated under reduced pressure (2 kPa) at a temperature of about 40° C

Sources & evidence

ORD record
ord-4cc758c6fca34efe876fe151f9c9d489
Source dataset
uspto-grants-2007_06
Patent number
US07227022B2

Reaction notes

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