Hydrochloric Acid → (3-Chloro-5-nitrophenyl)methanol

HRID 2303990Notes

Reaction equation

HRID 2303990 reaction equation
N[C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([N+:10]([O-:12])=[O:11])[CH:9]=1)[CH2:5][OH:6].N([O-])=O.[Na+].CCOC(C)=O.[ClH:23]>O.[Cu](Cl)Cl.[Cu]Cl>[Cl:23][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([N+:10]([O-:12])=[O:11])[CH:9]=1)[CH2:5][OH:6]

Participants

8

Reactant 4

HCID 313Hydrochloric Acid2×HCID 8857Ethyl AcetateHCID 15540036(3-Amino-5-nitrophenyl)methanolHCID 23668193Sodium Nitrite

Product 1

HCID 52987794(3-Chloro-5-nitrophenyl)methanolYield 70%

Reagents, catalysts & solvents 3

HCID 24014Cupric ChlorideCatalystHCID 62652Cuprous chlorideCatalystHCID 962WaterSolvent

Conditions

Temperature
-5 °C

Procedure

To a suspension of 3-amino-5-nitrobenzyl alcohol (103.8 g, 0.62 mol; from step (ii) above) in 1.0 L of 6N HCl at −5° C. was added sodium nitrite (47.1 g, 0.68 mol) in H2O (400 mL) over 45 min. The resulting solution was stirred at −5° C. for 1 h prior to the addition of a mixture of copper(II)chloride (125.0 g, 0.93 mol) and copper(I)chloride (0.74 g, 0.007 mol) in 6N HCl (1.0 L) over 1 h while maintaining the temperature at less than 0° C. The resulting solution was warmed to 60-70° C. for 2.5 h then cooled to room temperature and extracted with Et2O (6×). The organics were washed with brine (2×), dried (Na2SO4), filtered and concentrated in vacuo to give the crude product. Flash chromatography on silica gel eluting with Hex:EtOAc (4:1) gave 81.7 g (70%) of the sub-title compound as an off white solid. The sub-title compound could be further purified by crystallization from CH2Cl2.

Workup

  1. temperaturewhile maintaining the temperature at less than 0° C
  2. temperatureThe resulting solution was warmed to 60-70° C. for 2.5 h
  3. temperaturethen cooled to room temperature
  4. extractionextracted with Et2O (6×)
  5. washThe organics were washed with brine (2×)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give the crude product

Sources & evidence

ORD record
ord-99c07d08cc9f48fea137f7c5b738dc07
Source dataset
uspto-grants-2002_08
Patent number
US06433186B1

Reaction notes

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