Acetic Acid → HCID 49787391, compound

HRID 415371Notes

Reaction equation

HRID 415371 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([O:21][CH3:22])=[C:7]([CH:20]=1)[O:8][CH:9]1[CH2:14][CH2:13][N:12]([CH2:15][C:16]([NH:18][CH3:19])=[O:17])[CH2:11][CH2:10]1)#[N:2].C(O)(=O)C.S(=O)(=O)(O)O.[N+:32]([O-])([OH:34])=[O:33].N.C(#N)CC>[N+]([O-])(O)=O.O>[C:1]([C:3]1[C:4]([N+:32]([O-:34])=[O:33])=[CH:5][C:6]([O:21][CH3:22])=[C:7]([CH:20]=1)[O:8][CH:9]1[CH2:10][CH2:11][N:12]([CH2:15][C:16]([NH:18][CH3:19])=[O:17])[CH2:13][CH2:14]1)#[N:2]

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 222AmmoniaHCID 944Nitric AcidHCID 1118Sulfuric Acid2×HCID 7854Propionitrile2×HCID 49787392HCID 49787392, compound

Product 1

HCID 49787391HCID 49787391, compoundYield 82%

Reagents, catalysts & solvents 2

HCID 944Nitric AcidCatalystHCID 962WaterSolvent

Conditions

Temperature
5 °C

Procedure

2-[4-(5-Cyano-2-methoxyphenoxy)piperidin-1-yl]-N-methylacetamide (4, 8.78 g, 26.11 mmoles) was suspended in acetic acid (22.82 g, 364.87 mmoles) and the resulting reaction mixture cooled to 5° C. To this was added sulfuric acid (23.64 g, 234.95 mmoles) maintaining the reaction temperature below 30° C. To the resulting solution was added nitric acid (2.40 g, 26.63 mmoles). The reaction mixture was then heated to 35° C. and held for 3 hours. Additional nitric acid (117 mg, 1.31 mmoles) and sulphuric acid (1.31 g 13.1 mmoles) were charged and the reaction mixture was heated at 35° C. for 30 minutes. The solution was cooled to 20° C. and quenched with aqueous ammonia (92.45 g 1.36 moles), resulting in an increase in temperature to 50° C. To the resulting slurry was added, propionitrile (61.58 g 1.12 moles) and water (19 g). The reaction mixture was heated to 80° C. resulting in a clear solution, which upon settling gave two layers. The bottom layer was removed. The reaction mixture was cooled to 20° C. resulting in a thick slurry. The solid was isolated by filtration, washed with propionitrile (6.16 g 112.0 mmoles) and dried to afford the title compound (7.44 g, 82% yield); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.72 (m, 2H) 1.97 (m, 2H) 2.35 (m, 2H) 2.61 (d, J=4.7 Hz, 3H) 2.66 (m, 2H) 2.90 (s, 2H) 3.96 (s, 3H) 4.73 (tt, J=8.4, 4.0 Hz, 1H) 7.71 (q, J=4.7 Hz, 1H) 7.82 (s, 1H) 7.86 (s, 1H). Mass Spectrum: m/z (M+H)+ 349.2

Workup

  1. customthe resulting reaction mixture
  2. temperaturemaintaining the reaction temperature below 30° C
  3. temperatureThe reaction mixture was then heated to 35° C.
  4. temperaturethe reaction mixture was heated at 35° C. for 30 minutes
  5. temperatureThe solution was cooled to 20° C.
  6. customresulting in
  7. temperaturean increase in temperature to 50° C
  8. additionTo the resulting slurry was added
  9. temperatureThe reaction mixture was heated to 80° C.
  10. customresulting in a clear solution, which
  11. customupon settling gave two layers
  12. customThe bottom layer was removed
  13. temperatureThe reaction mixture was cooled to 20° C.
  14. customresulting in a thick slurry
  15. customThe solid was isolated by filtration
  16. customdried

Sources & evidence

ORD record
ord-6208020232ab4a369f32f2b74784669e
Source dataset
uspto-grants-2012_01
Patent number
US08088782B2

Reaction notes

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