Carbon Dioxide → 6-Chloro-2-methoxypyridine-3-carbaldehyde
Reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH3:9])[N:3]=1.C([Li])(C)(C)C.CN(C)[CH:17]=[O:18].C(=O)=O>O1CCCC1>[Cl:1][C:2]1[N:3]=[C:4]([O:8][CH3:9])[C:5]([CH:17]=[O:18])=[CH:6][CH:7]=1Participants
Procedure
To 2-Chloro-6-methoxypyridine (25, 0.511 g, 3.56 mmol) in tetrahydrofuran (10 mL) cooled in a −78° C. acetone/dry ice bath was added tert-butyllithium (1.7M in pentane, 5.0 mL, 7.66 mmol). The reaction was allowed to stir for 1 hour. Dimethylformamide (0.673 mL, 17.4 mmol) was added and the reaction was allowed to continue for an additional 30 minutes at −78° C., then stirred for 30 minutes outside of the dry-ice bath. The reaction was placed back in the dry-ice bath and quenched with 6 N HCl (1.5 mL) followed by water and allowed to warm to room temperature. The reaction was extracted with diethyl ether and aqueous (1M) sodium bicarbonate. The organic layer was separated, dried with anhydrous magnesium sulfate, filtered and volatiles removed by rotary evaporation, and the resulting yellow solid was dried under vacuum to provide 561 mg of compound 26 (3.27 mmol, 92% yield). MS (ESI) [M+H+]+=172.0.
Workup
- waitto continue for an additional 30 minutes at −78° C.
- customquenched with 6 N HCl (1.5 mL)
- extractionThe reaction was extracted with diethyl ether and aqueous (1M) sodium bicarbonate
- customThe organic layer was separated
- dry with materialdried with anhydrous magnesium sulfate
- filtrationfiltered
- customvolatiles removed by rotary evaporation
- customthe resulting yellow solid was dried under vacuum
Sources & evidence
- ORD record
- ord-bc519ffacd4a4a96b5ac625109350280
- Source dataset
- uspto-grants-2014_05
- Patent number
- US08722702B2
Reaction notes
Loading…