Boron Trichloride → 2'-Amino-3'-methyl-4'-methoxyacetophenone

HRID 553440Notes

Reaction equation

HRID 553440 reaction equation
C(C1N=C(C2[CH:18]=[C:17](Cl)[C:16]3[C:11](=[C:12]([CH3:22])[C:13]([O:20][CH3:21])=[CH:14][CH:15]=3)[N:10]=2)SC=1)(C)C.C[O:24]C1C(C)=C(C=CC=1)N.B(Cl)(Cl)Cl.[Cl-].[Cl-].[Cl-].[Al+3]>C(#N)C>[CH3:22][C:12]1[C:13]([O:20][CH3:21])=[CH:14][CH:15]=[C:16]([C:17](=[O:24])[CH3:18])[C:11]=1[NH2:10]

Participants

6

Reactant 4

HCID 25135Boron TrichlorideHCID 6451240Aluminum(III) ChlorideHCID 118048223-Methoxy-2-methylanilineHCID 513586512-(4-Chloro-7-methoxy-8-methylquinolin-2-yl)-4-isopropylthiazole

Product 1

HCID 250673162'-Amino-3'-methyl-4'-methoxyacetophenone

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Optionally substituted 2-(thiazol-2-yl)-4-chloro-7-alkoxy-8-alkyl-quinoline 2-phenyl-4-chloro-7-alkoxy-quinolines, such as 2-(4-isopropylthiazol-2-yl)-4-chloro-7-methoxy-8-methyl-quinoline, can be synthesized as shown in Scheme XIII. 3-Alkoxy-2-alkyl-anilines, such as 3-methoxy-2-methyl-aniline, can react with acetonitrile (CH3CN) in the presence of Lewis acids, for example boron trichloride and aluminum trichloride, to provide 2-alkyl-3-alkoxy-6-acetyl-anilines such as 2-methyl-3-methoxy-6-acetyl-aniline. The 2-alkyl-3-alkoxy-6-acetyl-anilines, such as 2-methyl-3-methoxy-6-acetyl-aniline, can be coupled to an an optionally substituted thiazole-2-carboxylic acid chloride, such as 4-isopropylthiazole-2-carbonyl chloride to provide an optionally substituted 1-acetyl-2-[(thiazol-2-yl)-carbonylamino]-3-alkyl-4-alkoxy-benzene, such as 1-acetyl-2-[(4-isopropyl-thiazol-2-yl)-carbonylamino]-3-methyl-4-methoxy-benzene. The optionally substituted 1-acetyl-2-[(thiazol-2-yl)-carbonylamino]-3-alkyl-4-alkoxy-benzene, such as 1-acetyl-2-[(4-isopropyl-thiazol-2-yl)-carbonylamino]-3-methyl-4-methoxy-benzene, can be cyclized under basic conditions, for example sodium tert-butoxide in tert-butanol, to provide an optionally substituted 2-(thiazol-2-yl)-4-hydroxy-7-alkoxy-8-alkyl-quinoline, such as 2-(4-isopropylthiazol-2-yl)-4-hydroxy-7-methoxy-8-methyl-quinoline. Finally, an optionally substituted 2-(thiazol-2-yl)-4-hydroxy-7-alkoxy-8-alkyl-quinoline, such as 2-(4-isopropylthiazol-2-yl)-4-hydroxy-7-methoxy-8-methyl-quinoline can be reacted with a chlorinating agent, for example phosphorous oxychloride, oxalyl chloride, thionyl chloride and the like, to provide an optionally substituted 2-(thiazol-2-yl)-4-chloro-7-alkoxy-8-alkyl-quinoline 2-phenyl-4-chloro-7-alkoxy-quinolines, such as 2-(4-isopropylthiazol-2-yl)-4-chloro-7-methoxy-8-methyl-quinoline.

Sources & evidence

ORD record
ord-b91101bcb86743089cad35816707822a
Source dataset
uspto-grants-2011_11
Patent number
US08048862B2

Reaction notes

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