Water → Methyl 3-amino-5-chloro-2-ethylbenzoate

HRID 1959290Notes

Reaction equation

HRID 1959290 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N+:14]([O-])=O)[C:5]([CH2:12][CH3:13])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[Cl-].[NH4+].O>CO.[Fe]>[NH2:14][C:4]1[C:5]([CH2:12][CH3:13])=[C:6]([CH:11]=[C:2]([Cl:1])[CH:3]=1)[C:7]([O:9][CH3:10])=[O:8]

Participants

6

Reactant 3

HCID 962WaterHCID 25517Ammonium ChlorideHCID 70872923Methyl 5-chloro-2-ethyl-3-nitrobenzoate

Product 1

HCID 86672668Methyl 3-amino-5-chloro-2-ethylbenzoateYield 44.7%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of methyl 5-chloro-2-ethyl-3-nitrobenzoate (6.18 g, 25.36 mmol) in Methanol (250 ml) at room temperature was added ammonium chloride (13.31 g, 253.65 mmol) followed by deionized Water (125 ml). The mixture was heated to 70° C. in air before the addition of iron (8.5 g, 152.19 mmol). The reaction turned to a dark color over the 2.5 hours it was stirred at 70° C. This mixture was allowed to cool to room temperature and was filtered through Kieselgel. The filter pad was washed with MeOH (250 ml) and the filtrate concentrated under reduced pressure. The residue was dissolved in saturated NaHCO3(aq) (50 ml) and EtOAc (150 ml). The phases were separated and the organic phase was washed with saturated NaHCO3(aq) (2×50 ml) before being dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by FCC (50 g silica, Isolute cartridge, gradient of eluents; 95:5 Heptane:EtOAc to 75:25 Heptane:EtOAc) to give 2.42 g (22%, 7% corrected yields) of methyl 3-amino-5-chloro-2-ethylbenzoate as a yellow oil. The product contains ˜25% ethyl ester and possible ˜15% 4-nitro products. The material was taken through the next step without further purification. LC-MS 31%, 2.00 min (3 minute LC-MS method), m/z=295.0, 1H NMR (500 MHz, Chloroform-d) δ ppm 7.17 (d, J=2.1 Hz, 1H), 6.79 (d, J=2.1 Hz, 1H), 3.87 (s, 3H), 3.86-3.81 (m, 2H), 2.74 (q, J=7.5 Hz, 2H), 1.20 (t, J=7.5 Hz, 3H).

Workup

  1. customturned to a dark color over the 2.5 hours it
  2. temperatureto cool to room temperature
  3. filtrationwas filtered through Kieselgel
  4. washThe filter pad was washed with MeOH (250 ml)
  5. concentrationthe filtrate concentrated under reduced pressure
  6. dissolutionThe residue was dissolved in saturated NaHCO3(aq) (50 ml)
  7. customThe phases were separated
  8. washthe organic phase was washed with saturated NaHCO3(aq) (2×50 ml)
  9. dry with materialbefore being dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by FCC (50 g silica, Isolute cartridge, gradient of eluents; 95:5 Heptane:EtOAc to 75:25 Heptane:EtOAc)

Sources & evidence

ORD record
ord-e83904accd064cfcb0c09f32aec665a1
Source dataset
uspto-grants-2013_04
Patent number
US08410088B2

Reaction notes

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