3,5-Dimethylbenzenethiol → 6-Methoxyquinolin-3-amine

HRID 1756821Notes

Reaction equation

HRID 1756821 reaction equation
[N+:1]([C:4]1[CH:5]=[N:6][C:7]2[C:12]([CH:13]=1)=[CH:11][C:10]([O:14][CH3:15])=[CH:9][CH:8]=2)([O-:3])=[O:2].Cl.COC1C=CC(N)=CC=1.CC1C=C(S)C=C(C)C=1>C(O)(=O)C>[N+:1]([C:4]1[CH:5]=[N:6][C:7]2[C:12]([CH:13]=1)=[CH:11][C:10]([O:14][CH3:15])=[CH:9][CH:8]=2)([O-:3])=[O:2].[NH2:1][C:4]1[CH:5]=[N:6][C:7]2[C:12]([CH:13]=1)=[CH:11][C:10]([O:14][CH3:15])=[CH:9][CH:8]=2

Participants

6

Reactant 3

HCID 1175483,5-DimethylbenzenethiolHCID 15193946-Methoxy-3-nitroquinolineHCID 27349564-Anisidine hydrochloride

Product 2

HCID 5999396-Methoxyquinolin-3-amineYield 86%HCID 15193946-Methoxy-3-nitroquinoline

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

3-Hydroxy-6-methoxyquinoline is not, a known compound, and the common methods for synthesizing quinolines are not readily applicable to 3-hydroxy substituents. p-Anisidine hydrochloride was treated with sodium nitromalonaldehyde to give the enamine 13. Heating the enamine 13 in a mixture of acetic acid sulfolane gave 3-nitro-6-methoxyquinoline 14 (30%). The yield of 14 could be improved to 48%, by heating p-anisidine hydrochloride and the enamine 13 in acetic acid in the presence of a catalylic amount of 3,5dimethylthiophenol. Reduction of 14 using stannous chloride gave 3-amino-6methoxyquinoline 15 (86%). Standard diazotization conditions and hydrolysis gave the phenol 16 (95%). Treatment of 16 with t-butyldimethylsilyl chloride/imidazole/in dimethylformamide gave 17 (91%) (FIG. 6).

Sources & evidence

ORD record
ord-149f89d5fbe2402794d489bd5ac01a7b
Source dataset
uspto-grants-1995_08
Patent number
US05442065

Reaction notes

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