Potassium Hydroxide → HCID 22404755, compound

HRID 440648Notes

Reaction equation

HRID 440648 reaction equation
[C:1]([C:3]1[C:12]2[O:11][C:10]([CH3:14])([CH3:13])[CH:9]=[CH:8][C:7]=2[CH:6]=[CH:5][C:4]=1[F:15])#[N:2].[OH-:16].[K+]>C(O)(C)(C)C>[CH3:14][C:10]1([CH3:13])[CH:9]=[CH:8][C:7]2[CH:6]=[CH:5][C:4]([F:15])=[C:3]([C:1]([NH2:2])=[O:16])[C:12]=2[O:11]1

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 22404770HCID 22404770, compound

Product 1

HCID 22404755HCID 22404755, compound

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

Schema 6 illustrates the synthesis of an amino substituted 2,2-dialkyl-2H-1-benzopyran and an amino substituted 2,2-dialkyl-3,4-dihydro-2H-1-benzopyran, for example, 8-amino-5-chloro-7-fluoro-2H-1-benzopyran and 8-amino-5-chloro-3,4-dihydro-7-fluoro-2H-1-benzopyran by the reaction of an appropriately substituted 2-fluorobenzonitrile with 2-methyl-3-butyn-2-ol under basic conditions in dimethyl sulfoxide, yielding the corresponding 3-(2-cyano-substituted-phenoxy)-3-methyl-1-butyne (XXI). The butyne intermediate is then cyclized at 180° C. in 1,2-dichlorobenzene, giving the appropriate 8-cyano-2,2-dialkyl-7-fluoro-2H-1-benzopyran, for example, 8-cyano-2,2-dimethyl-7-fluoro-2H-1-benzopyran (XXII), which is in turn treated with potassium hydroxide in t-butanol, yielding 2,2-dimethyl-7-fluoro-2H-1-benzopyran-8-ylcarboxamide (XXIII). The so-prepared carboxamide is then reduced with sodium hypochlorite and sodium hydroxide in water and dioxane, affording the corresponding free amine, for example, 8-amino-2,2-dimethyl-7-fluoro-2H-1-benzopyran (XXIV). The intermediate benzopyran is optionally halogenated in the 5-position as described above, yielding the corresponding benzopyran intermediate, for example, 8-amino-5-chloro-2,2-dimethyl-7-fluoro-2H-1-benzopyran (XXV). To obtain an amino substituted 2,2-dialkyl-3,4-dihydro-2H-1-benzopyran, for example, 8-amino-5-chloro-3,4-dihydro-7-fluoro-2H-1-benzopyran, the benzopyran (XXIV), described above, is first hydrogenated in the presence of 5% palladium on carbon in ethanol. The so-prepared 8-amino-3,4-dihydro-7-fluoro-2H-1-benzopyran (XXVI) is then optionally halogenated in the 5-position, affording the desired 8-amino-5-chloro-3,4-dihydro-7-fluoro-2H-1-benzopyran (XXVII). Examples 13 and 14 provide detailed descriptions of how these compounds are prepared.

Sources & evidence

ORD record
ord-2e444328730348058c7d629f89b1a48b
Source dataset
uspto-grants-1996_05
Patent number
US05521147

Reaction notes

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