Hydrochloric Acid → 5-(tert-Butyl)-2-methoxy-3-nitroaniline

HRID 1423262Notes

Reaction equation

HRID 1423262 reaction equation
[C:1]([C:5]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[C:8]([O:14][CH3:15])=[C:7]([N+:16]([O-])=O)[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].CC1CCC=CC1.C(O)C.Cl>[Pd].O>[C:1]([C:5]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[C:8]([O:14][CH3:15])=[C:7]([CH:6]=1)[NH2:16])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 115724-Methylcyclohexene2×HCID 42526024-tert-Butyl-2,6-dinitroanisole

Product 1

HCID 112068635-(tert-Butyl)-2-methoxy-3-nitroaniline

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 962WaterSolvent

Procedure

Under N2 was charged 4-tert-butyl-2,6-dinitroanisole (620 g, 2.439 mol), IMS (4774 mL) and 10% Pd/C (31.8 g). The reaction mixture was heated to reflux (78° C.) and 4-methyl-1-cyclohexene (500 mL, 4.159 mol) was added dropwise over 4.5 h. The reaction was stirred at reflux overnight, whereupon HPLC analysis indicated 72.13% product and 27.17% starting material. Further 4-methyl-1-cyclohexene (160 mL, 1.331 mol) was added dropwise over 3 h and the reaction was stirred at reflux for 72 h. HPLC analysis indicated 92.72% product and 0% starting material. The reaction was cooled to room temperature and the catalyst was removed via vacuum filtration and washed with IMS (500 mL). The solvents were concentrated to ca. 1200 mL to give a ratio of 1:4.45 product:ethanol (target 1:5). 2 M HCl (124 mL) was charged dropwise to the remainder while maintaining the temperature below 23° C. Water (3100 mL) was charged and the resulting suspension was stirred at room temperature for 1.5 h. The solid was collected via vacuum filtration and washed with water (2×1000 mL). The resulting orange needles were dried, under vacuum, at 40° C. overnight. Yield=475.2 g (86.9%). Purity >97% by 1H NMR. HPLC purity 98.8%. KF 0.36%.

Workup

  1. temperatureThe reaction mixture was heated
  2. additionwas added dropwise over 4.5 h
  3. temperatureat reflux overnight, whereupon HPLC analysis
  4. stirringthe reaction was stirred
  5. temperatureat reflux for 72 h
  6. customthe catalyst was removed via vacuum filtration
  7. washwashed with IMS (500 mL)
  8. concentrationThe solvents were concentrated to ca. 1200 mL
  9. customto give a ratio of 1:4.45 product
  10. temperaturewhile maintaining the temperature below 23° C
  11. stirringthe resulting suspension was stirred at room temperature for 1.5 h
  12. filtrationThe solid was collected via vacuum filtration
  13. washwashed with water (2×1000 mL)
  14. customThe resulting orange needles were dried, under vacuum, at 40° C. overnight

Sources & evidence

ORD record
ord-8f26c9cc52b443709be53e1858697d73
Source dataset
uspto-grants-2015_01
Patent number
US08927563B2

Reaction notes

Loading…