Water → HCID 49787392, compound

HRID 1951996Notes

Reaction equation

HRID 1951996 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[CH:6][C:5]=1[O:12][CH:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.Cl[CH2:20][C:21]([NH:23][CH3:24])=[O:22].C(=O)([O-])[O-].[K+].[K+].O>C(#N)C>[C:8]([C:7]1[CH:10]=[CH:11][C:4]([O:3][CH3:2])=[C:5]([CH:6]=1)[O:12][CH:13]1[CH2:18][CH2:17][N:16]([CH2:20][C:21]([NH:23][CH3:24])=[O:22])[CH2:15][CH2:14]1)#[N:9]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 667732-chloro-N-methylacetamideHCID 57476870HCID 57476870, compound

Product 1

HCID 49787392HCID 49787392, compoundYield 96.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
20 °C

Procedure

4-Methoxy-3-(piperidin-4-yloxy)benzonitrile hydrochloride salt (3, 28.36 g, 95.82 mmoles), 2-chloro-N-methylacetamide (12.37 g, 114.98 mmoles) and potassium carbonate (33.11 g, 239.55 mmoles) were suspended in acetonitrile (161.36 g). The reaction mixture was heated at reflux for 3 hours. The reaction mixture was cooled to 20° C. and water (386.26 g) was charged. The reaction was heated to 75° C. and the volume reduced by distillation. Upon cooling crystallisation occurred. The resulting solid was isolated by filtration, washed twice with water (77.25 g and 128.75 g) and then dried to give the title compound (27.95 g, 94% yield); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.68 (m, 2H) 1.91 (m, 2H) 2.29 (m, 2H) 2.61 (d, J=4.7 Hz, 3H) 2.67 (m, 2H) 2.88 (s, 2H) 3.83 (s, 3H) 4.41 (tt, J=8.3, 4.0 Hz, 1H) 7.11 (d, J=8.4 Hz, 1H) 7.40 (dd, J=8.4, 1.9 Hz, 1 h) 7.47 (d, J=1.9 Hz, 1H) 7.68 (q, J=4.7 Hz, 1H); Mass Spectrum: m/z (M+H)+ 304.2.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 3 hours
  3. temperatureThe reaction was heated to 75° C.
  4. distillationthe volume reduced by distillation
  5. temperatureUpon cooling
  6. customcrystallisation
  7. customThe resulting solid was isolated by filtration
  8. washwashed twice with water (77.25 g and 128.75 g)
  9. customdried

Sources & evidence

ORD record
ord-518b4f62329e4a68a65ff9a7b78c7a48
Source dataset
uspto-grants-2013_03
Patent number
US08404839B2

Reaction notes

Loading…