Hydrochloric Acid → N-(2,5-Dimethoxyphenyl)-6-hydroxynaphthalene-1-carboxamide

HRID 1061845Notes

Reaction equation

HRID 1061845 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([C:12]([OH:14])=O)=[CH:7][CH:6]=[CH:5]2.S(Cl)(Cl)=O.[CH3:19][O:20][C:21]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:22]=1[NH2:23].C(N(CC)CC)C.Cl>O.C1COCC1>[CH3:19][O:20][C:21]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:22]=1[NH:23][C:12]([C:8]1[C:9]2[C:4](=[CH:3][C:2]([OH:1])=[CH:11][CH:10]=2)[CH:5]=[CH:6][CH:7]=1)=[O:14]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 76132,5-DimethoxyanilineHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 54638006-Hydroxy-1-naphthoic acid

Product 1

HCID 22285700N-(2,5-Dimethoxyphenyl)-6-hydroxynaphthalene-1-carboxamideYield 95.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 6-hydroxy-1-naphthoic acid (5.0 g, 26.6 mmol) and thionyl chloride (20 mL) was refluxed for 1 h. The volatiles were then removed under vacuum. The residue was dissolved in THF (20 mL) and added into a cold (0° C.) solution of 2,5-dimethoxyaniline (4.06 g, 26.6 mmol), triethylamine (10 mL, 71.8 mmol) and THF (100 mL). The mixture was stirred for 30 min, poured into water, acidified with HCl (2N) and extracted with EtOAc. The organic extracts were dried over MgSO4. Evaporation and purification by flash chromatography (hexanes/EtOAc 1/1) gave a tan solid (8.2 g, 95% yield, m.p. 165-166° C.); MS m/e 324 (M+H)+.

Workup

  1. temperaturewas refluxed for 1 h
  2. customThe volatiles were then removed under vacuum
  3. dissolutionThe residue was dissolved in THF (20 mL)
  4. extractionextracted with EtOAc
  5. dry with materialThe organic extracts were dried over MgSO4
  6. customEvaporation and purification by flash chromatography (hexanes/EtOAc 1/1)

Sources & evidence

ORD record
ord-28afe8fa9da74f028d4e3740ea33e32b
Source dataset
uspto-grants-2005_11
Patent number
US06960607B2

Reaction notes

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