Acetic Acid → 1303512-02-8

HRID 1050917Notes

Reaction equation

HRID 1050917 reaction equation
[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][N:7]2[CH:12]=[CH:11][CH:10]=[C:9]([OH:13])[C:8]2=[O:14])=[CH:4][CH:3]=1.[N:17]1([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1.C=O.[C:32](O)(=O)C>C(O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[CH:12]=[CH:11][C:10]([CH2:32][N:20]3[CH2:21][CH2:22][N:17]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:18][CH2:19]3)=[C:9]([OH:13])[C:8]2=[O:14])=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 143452tert-Butyl piperazine-1-carboxylateHCID 529122191-(4-chlorobenzyl)-3-hydroxypyridin-2(1H)-one

Product 1

HCID 529122181303512-02-8Yield 83.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
50 °C

Procedure

to a nitrogen purged 2-L round bottom flask equipped with a mechanical stirrer, upright condenser, and thermometer was charged 1-(4-chlorobenzyl)-3-hydroxypyridin-2(1H)-one (1) (50.0 g, 0.21 mol, 1 equiv.), tert-butyl piperazine-1-carboxylate, (2) (79.0 g, 0.42 mol, 2 equiv.) [CAS No. 57260-71-6] and ethanol (750 mL, 15 parts v/w). The solution was stirred and 37% aqueous formaldehyde (34.7 mL, 0.47 mol, 2.2 equiv.) and acetic acid (36.4 mL, 0.64 mol, 3 equiv.) were added and the solution stirred for 1 hour after which the reaction solution was heated to 50° C. for 18 hours. The reaction mixture was then cooled below room temperature and filtered under vacuum. The resulting solid was rinsed with ethanol (250 mL) and dried under a stream of nitrogen to afford 77.2 g (83.9%) of the desired product. 1H NMR (DMSO-d6) δ ppm 7.4 (d, 2H), 7.3 (d, 2H), 7.2 (d, 1H), 6.2 (d, 1H), 5.1 (s, 2H), 3.4-3.2 (m partly under brs water peak, 6H), 2.3 (m, 4H), 1.4 (s, 9H).13C NMR (DMSO-d6) [observed] δ ppm 157.24, 153.77, 144.36, 136.33, 132.15, 129.67, 128.48, 126.86, 124.56, 107.01, 78.74, 54.68, 52.49, 50.64, 43.48, and 28.03.

Workup

  1. customto a nitrogen purged 2-L round bottom flask
  2. customequipped with a mechanical stirrer
  3. stirringthe solution stirred for 1 hour after which the reaction solution
  4. temperatureThe reaction mixture was then cooled below room temperature
  5. filtrationfiltered under vacuum
  6. washThe resulting solid was rinsed with ethanol (250 mL)
  7. customdried under a stream of nitrogen

Sources & evidence

ORD record
ord-1c18bfedd7b644caa5a7af68cd23e91e
Source dataset
uspto-grants-2016_07
Patent number
US09388135B2

Reaction notes

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