Hydrochloric Acid → 3,5-Dimethyl-4-(4'-methoxy-3'-iso-propylphenoxy)-phenyl hydrazine

HRID 1171017Notes

Reaction equation

HRID 1171017 reaction equation
[N:1]([O-])=O.[Na+].[CH3:5][C:6]1[CH:7]=[C:8]([CH:10]=[C:11]([CH3:25])[C:12]=1[O:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([CH:22]([CH3:24])[CH3:23])[CH:15]=1)[NH2:9].Cl.[Sn](Cl)Cl>O.C(O)C>[CH3:25][C:11]1[CH:10]=[C:8]([NH:9][NH2:1])[CH:7]=[C:6]([CH3:5])[C:12]=1[O:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([CH:22]([CH3:23])[CH3:24])[CH:15]=1

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 24479Stannous ChlorideHCID 100167993,5-Dimethyl4-(3'-isopropyl-4'-methoxyphenoxy)-anilineHCID 23668193Sodium Nitrite

Product 1

HCID 666428773,5-Dimethyl-4-(4'-methoxy-3'-iso-propylphenoxy)-phenyl hydrazineYield 45.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 962WaterSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of sodium nitrite (155 mg, 2.24 mmol) in water (1 mL) was added to a suspension of 3,5-dimethyl-4-(4′-methoxy-3′-iso-propylphenoxy)-aniline (J. Med. Chem. 1995, 38, 695, 640 mg, 2.24 mmol) in ethanol (3 mL) and concentrated hydrochloric acid (12 M, 1.12 mL, 13.44 mmol) at 0° C. The yellow heterogeneous solution slowly turns to an orange clear solution. After stirring at 0° C. for 30 minutes, a solution of tin dichloride (1.53 g, 8.06 mmol) in hydrochloric acid (12 M, 1.3 mL, 15.68 mmol) was added. The orange solution turned green and a white precipitate formed. Ethanol (3 mL) was added to dissolve most of the precipitate and the heterogeneous reaction mixture was stirred at 0° C. After 2 hours, water was added and the precipitate collected by filtration. The sticky solid was dissolved in ethyl acetate and washed with water, 1 N sodium hydroxide then brine. The organics were dried over sodium sulfate, concentrated under reduced pressure and the residue was purified by column chromatography (silica gel, dichloromethane/methanol 95/5 to 90/10) to give 3,5-dimethyl-4-(4′-methoxy-3′-iso-propylphenoxy)-phenyl hydrazine (305 mg, 45%): 1H NMR (300 MHz, CDCl3) δ 6.77 (d, J=3.0 Hz, 1H), 6.67 (d, J=9.0 Hz, 1H) 6.58 (s, 2H), 6.37 (dd, J=9.0, 3.0 Hz, 1H), 3.77 (s, 3H), 3.27 (heptuplet, J=6.9 Hz, 1H), 2.09 (s, 3H), 1.18 (d, J=6.9 Hz, 6H); TLC conditions: Merck silica gel, 250 microns; Mobile phase=dichloromethane-methanol (9:1), Rf=0.6.

Workup

  1. customa white precipitate formed
  2. dissolutionto dissolve most of the precipitate
  3. stirringthe heterogeneous reaction mixture was stirred at 0° C
  4. waitAfter 2 hours
  5. filtrationthe precipitate collected by filtration
  6. dissolutionThe sticky solid was dissolved in ethyl acetate
  7. washwashed with water, 1 N sodium hydroxide
  8. dry with materialThe organics were dried over sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customthe residue was purified by column chromatography (silica gel, dichloromethane/methanol 95/5 to 90/10)

Sources & evidence

ORD record
ord-02e1a76ed9364d2785f5f946afd88280
Source dataset
uspto-grants-2010_11
Patent number
US07829552B2

Reaction notes

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