Hydrochloric Acid → HCID 49787390, compound

HRID 1951998Notes

Reaction equation

HRID 1951998 reaction equation
[C:1]([C:3]1[C:4]([N+:23]([O-])=O)=[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].S(S([O-])=O)([O-])=O.[Na+].[Na+].Cl.[OH-].[Na+].CC1CCCO1>O.CO>[NH2:23][C:4]1[C:3]([C:1]#[N:2])=[CH:20][C:7]([O:8][CH:9]2[CH2:10][CH2:11][N:12]([CH2:15][C:16]([NH:18][CH3:19])=[O:17])[CH2:13][CH2:14]2)=[C:6]([O:21][CH3:22])[CH:5]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 73012-MethyltetrahydrofuranHCID 14798Sodium HydroxideHCID 24489Sodium DithioniteHCID 49787391HCID 49787391, compound

Product 1

HCID 49787390HCID 49787390, compoundYield 87.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

2-[4-(5-Cyano-2-methoxy-4-nitrophenoxy)piperidin-1-yl]-N-methylacetamide (5, 7.42 g, 19.38 mmoles) was suspended in water (44.52 g) and methanol (5.35 g). To this was added sodium dithionite (11.91 g, 58.15 mmoles) and the resulting reaction mixture was heated to 60° C. To the reaction mixture was added hydrochloric acid (46.98 g, 463.89 mmoles)), resulting in a solution, which was held at 60° C. for 3 hours. The reaction mixture was then allowed to cool to 20° C. Aqueous sodium hydroxide (15.51 g 182.2 mmoles) was charged followed by 2-methyltetrahydrofuran (58.0 g). The reaction mixture was heated to 60° C., which upon settling gave two layers and the lower aqueous layer was discarded. The volume of the reaction mixture was reduced by vacuum distillation and methyl tert-butyl ether (18.54 g) was added to give a slurry which was cooled to 10° C. and then the solid was collected by filtration. The solid was washed with 2-methyltetrahydrofuran (5.8 g) and dried to give the title compound (5.4 g, 78% yield); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.62 (m, 2H) 1.82 (m, 2H) 2.20 (m, 2H) 2.60 (d, J=4.7 Hz, 3H) 2.65 (m, 2H) 2.86 (s, 2H) 3.72 (s, 3H) 4.00 (tt, J=8.3, 4.0 Hz, 1H) 5.66 (br. s, 2H) 6.39 (s, 1H) 6.94 (s, 1H) 7.65 (q, J=4.7 Hz, 1H)

Workup

  1. customthe resulting reaction mixture
  2. customresulting in a solution, which
  3. temperatureto cool to 20° C
  4. temperatureThe reaction mixture was heated to 60° C.
  5. customwhich upon settling gave two layers
  6. distillationThe volume of the reaction mixture was reduced by vacuum distillation and methyl tert-butyl ether (18.54 g)
  7. additionwas added
  8. customto give a slurry which
  9. temperaturewas cooled to 10° C.
  10. filtrationthe solid was collected by filtration
  11. washThe solid was washed with 2-methyltetrahydrofuran (5.8 g)
  12. customdried

Sources & evidence

ORD record
ord-4a7d4b985d114a0aba0d7df3afe9413d
Source dataset
uspto-grants-2013_03
Patent number
US08404839B2

Reaction notes

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