Hydrochloric Acid → HCID 86645334, compound

HRID 1850424Notes

Reaction equation

HRID 1850424 reaction equation
[N:1]([O-])=O.[Na+].Cl.[N+:6]([C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=1)([O-:8])=[O:7].[CH3:16][O:17][C:18]1[C:26]2[O:25][C:24]([CH3:28])([CH3:27])[CH2:23][C:22]=2[C:21]([CH3:29])=[CH:20][C:19]=1[CH3:30]>C(O)(=O)C.O>[CH3:16][O:17][C:18]1[C:26]2[O:25][C:24]([CH3:27])([CH3:28])[CH2:23][C:22]=2[C:21]([CH3:29])=[C:20]([N:1]=[N:13][C:12]2[CH:14]=[CH:15][C:9]([N+:6]([O-:8])=[O:7])=[CH:10][CH:11]=2)[C:19]=1[CH3:30]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 74754-NitroanilineHCID 23668193Sodium NitriteHCID 66760033HCID 66760033, compound

Product 1

HCID 86645334HCID 86645334, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
10 °C

Procedure

A solution of water (100 mL) containing sodium nitrite (61.8 g, 895 mmol) was added dropwise to a suspension of 6N hydrochloric acid (1.74 L) containing p-nitroaniline (129 g, 933 mmol) under ice-cooling condition, with the inner temperature thereof being maintained at 10° C. or lower. The reaction solution was stirred under ice-cooling condition for 1 hour, and after that, a solution of acetic acid (1.74 L) containing 7-methoxy-2,2,4,6-tetramethyl-2,3-dihydro-1-benzofuran (crude, calculated as 746 mmol) synthesized in Reference Example 93 was added dropwise thereto. The obtained mixture was stirred at 45° C. for 4 hours. After cooled to room temperature, the precipitated solid was collected by filtration, and it was washed with 50% acetic acid aqueous solution (500 mL), water (500 mL) and cold methanol (500 mL) to give 1-(7-methoxy-2,2,4,6-tetramethyl-2,3-dihydro-1-benzofuran-5-yl)-2-(4-nitrophenyl)diazene as wet crystal. Sodium hydrosulfite (519 g, 2.98 mol) was added to a suspension of methanol (1.74 L)/water (580 mL) containing the obtained wet crystal (calculated as 746 mmol), and the mixture was refluxed for 2 hours. After cooled to room temperature, the precipitate was filtered. Saturated saline was added to the filtrate, and extraction was performed using ethyl acetate (1.5 L, 1 L). The organic layer was washed with saturated saline (1 L) and dried using anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate 85:15-70:30). The obtained crude product was dissolved in ethyl acetate (1.74 L), and 4N hydrochloric acid/ethyl acetate (100 mL) was added thereto for conversion into hydrochloride salt. The obtained white solid was collected by filtration, and it was washed with ethyl acetate to give 87.7 g of the title compound as a white solid (yield: 46%).

Workup

  1. temperaturecooling condition
  2. temperaturecooling condition for 1 hour
  3. customsynthesized in Reference Example 93
  4. additionwas added dropwise
  5. stirringThe obtained mixture was stirred at 45° C. for 4 hours
  6. temperatureAfter cooled to room temperature
  7. filtrationthe precipitated solid was collected by filtration, and it
  8. washwas washed with 50% acetic acid aqueous solution (500 mL), water (500 mL) and cold methanol (500 mL)

Sources & evidence

ORD record
ord-ddb0769263704f26ae39b1d84446f08b
Source dataset
uspto-grants-2015_02
Patent number
US08957069B2

Reaction notes

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