4-Hydroxybenzaldehyde → 4-{[tert-Butyl(dimethyl)silyl]oxy}benzaldehyde
Reaction equation
[OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.[CH3:10][C:11]([Si:14](Cl)([CH3:16])[CH3:15])([CH3:13])[CH3:12].N1C=CN=C1>CN(C)C=O>[CH3:10][C:11]([Si:14]([CH3:16])([CH3:15])[O:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1)([CH3:13])[CH3:12]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
When the substituent R1 was methylsulfonyloxy or trifluoromethylsulfonyloxy, a number of additional synthesis steps were needed to obtain the hydrazone (I). The intermediate 4-hydroxybenzaldehyde was reacted with (1,1-dimethylethyl)dimethylsilyl chloride and imidazole in dimethylformamide to afford 4-[(I,1-dimethylethyl)dimethylsilyloxy]benzaldehyde. With the hydroxy substituent protected, the benzaldehyde was reacted by methods described above with the 5-bromo-2,2-difluoro-1,3-benzodioxole to afford the corresponding alcohol which was in turn converted to the ketone. Reaction of the resulting [[4-(1,1-dimethylethyl)dimethylsilyloxy]phenyl](2,2-difluoro-1,3-benzodioxol-5-yl) ketone with tetrabutylammonium fluoride in tetrahydrofuran cleaved the (1,1-dimethylethyl)dimethylsilyl substituent to yield (4-hydroxyphenyl)(2,2-difluoro-1,3-benzodiox-5-yl) ketone. The 4-hydroxy intermediate was reacted with methanesulfonyl chloride or trifluoromethanesulfonic anhydride by methods described above to yield the corresponding (4-methylsulfonyloxyphenyl)- or (4-trifluoromethylsulfonyloxyphenyl)(2,2-difluoro-1,3-benzodioxol-5yl) ketone. The ketone was then converted to the hydrazone (I) as described above. Example 4 illustrates this route.
Workup
- customa number of additional synthesis steps
Sources & evidence
- ORD record
- ord-549b17a968054b62ba1e0f1c39bf2d94
- Source dataset
- uspto-grants-1990_01
- Patent number
- US04895871
Reaction notes
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