Acetic Anhydride → 3-Cyano-2-(4-methylphenyl)pyridine
Reaction equation
Br[C:2]1[C:7]([C:8]#[N:9])=[CH:6][CH:5]=[CH:4][N:3]=1.C(OC(=O)C)(=O)C.[CH3:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1>>[C:8]([C:7]1[C:2]([C:21]2[CH:22]=[CH:23][C:18]([CH3:17])=[CH:19][CH:20]=2)=[N:3][CH:4]=[CH:5][CH:6]=1)#[N:9]Participants
Procedure
Synthetic Scheme XXV shows the 8-step preparation of the alkylating reagent 2-(4-bromomethylphenyl)-3-cyanopyridine (53) from 2-amino-3-picoline (54) (Aldrich). In step 1, the aminopicoline 54 was converted to the bromopicoline 55 by reaction with bromine, concentrated hydrobromic acid, and sodium nitrite at 0° C. In step 2, the picoline 55 was oxidized with KMNO4 to give the corresponding carboxylic acid 56. In step 3, the acid 56 was reduced to the alcohol 57 with borane/THF. In step 4, the alcohol 57 was oxidized to the aldelyde 58 under Swern conditions or by using MnO2. In step 5, the aldehyde 58 was reacted with hydroxylamine to give the oxime 59. In step 6, the oxime 59 was converted to 2-bromo-3-cyanopyridine (60) with acetic anhydride at reflux. In step 7, the nitrile 60 was coupled with 4-methylphenylboronic acid (52) (Scheme XXIV) using Snieckus conditions (Scheme XIII) to give 3-cyano-2-(4-methylphenyl)pyridine (61). In step 8, 61 was brominated with NBS/AIBN in carbon tetrachloride at reflux to give the desired alkylating reagent 53. ##STR79##
Workup
- temperatureat reflux
Sources & evidence
- ORD record
- ord-c73b9244a7e44955a80f22137fdfb742
- Source dataset
- uspto-grants-1997_02
- Patent number
- US05602153
Reaction notes
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