Phosphorus oxide (P4O10) → 3-(p-Tolyl)isonicotinonitrile
Reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[C:8]#[N:9].O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.[CH3:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1>>[C:8]([C:7]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[C:28]1[CH:29]=[CH:30][C:25]([CH3:24])=[CH:26][CH:27]=1)#[N:9]Participants
Procedure
Synthetic Scheme XXVI shows the 6-step preparation of the alkylating reagent 3-(4-bromomethylphenyl)-4-cyanopyridine (62) from 4-picoline (63) (Aldrich). In step 1, 4-picoline was brominated with bromine in fuming sulfuric acid at high temperatures to give 3-bromo-4-picoline (64). In step 2, the picoline 64 was oxidized to the corresponding carboxylic acid 65 with KMnO4. In step 3, the acid 65 was first converted to its acid chloride with oxalyl chloride and subsequently treated with condensed ammonia to give the amide 66. In step 4, the amide 66 was converted to 3-bromo-4-cyanopyridine (67) by treatment with P2O5 at high temperatures. In step 5, the nitrile 67 was coupled with 4-methylphenylboronic acid (52) (Scheme XXIV) using Snieckus conditions (Scheme XIII) to give 4-cyano-3-(4-methylphenyl)pyridine (68). In step 6, 68 was brominated with NBS/AIBN in carbon tetrachloride at reflux to give the desired alkylating reagent 62. ##STR80##
Sources & evidence
- ORD record
- ord-a96a40678b3c4368bb36b6de747acdb9
- Source dataset
- uspto-grants-1997_02
- Patent number
- US05602153
Reaction notes
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