Dimethylformamide → 6-Chloro-3-Methylpicolinaldehyde

HRID 1854603Notes

Reaction equation

HRID 1854603 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=1.[Li]CCCC.[Br:14][C:15]1[C:20]([CH3:21])=[CH:19][CH:18]=[C:17]([Cl:22])[N:16]=1.CN([CH:26]=[O:27])C>C1COCC1>[Br:14][C:15]1[C:20]([CH3:21])=[CH:19][CH:18]=[C:17]([Cl:22])[N:16]=1.[Cl:1][C:2]1[N:3]=[C:4]([CH:26]=[O:27])[C:5]([CH3:8])=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 5813932-Chloro-5-methyl-pyridineHCID 534166752-Bromo-6-chloro-3-methylpyridineHCID 178418339Butyllithium

Product 2

HCID 193617266-Chloro-3-MethylpicolinaldehydeYield 45%HCID 534166752-Bromo-6-chloro-3-methylpyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

2-Bromo-6-chloro-3-methyl-pyridine was prepared from 2-chloro-5-methylpyridine by by the method of Gros P. and Fort Y. (J. Org. Chem., 2005, 8220). A solution of n-BuLi (1.6M in hexanes) (2.0 ml, 3.30 mmol) in dry THF (6 ml) at −78° C. under argon was treated dropwise with a solution of 2-bromo-6-chloro-3-methyl-pyridine (642 mg, 3.10 mmol) in dry THF (4 ml) and stirred at this temperature for 30 minutes. A solution of DMF (385 μl, 4.70 mmol) in dry THF (1 ml) was added dropwise and stirred at −78° C. for a further 45 minutes before warming to ambient temperature. The reaction was quenched with MeOH (3 ml), treated with water and extracted with EtOAc. The combined organics were dried over MgSO4, filtered and evaporated under reduced pressure before purification by column chromatography on SiO2, eluting with 2% EtOH in DCM to afford 6-chloro-3-methyl-pyridine-2-carbaldehyde as a yellow solid (217 mg, 45%). 1H NMR (400 MHz, CDCl3) δ 10.09 (s, 1H), 7.60 (d, J=7.7 Hz, 1H), 7.42 (d, J=7.7 Hz, 1H), 2.64 (s, 3H).

Workup

  1. stirringstirred at −78° C. for a further 45 minutes
  2. customThe reaction was quenched with MeOH (3 ml)
  3. additiontreated with water
  4. extractionextracted with EtOAc
  5. dry with materialThe combined organics were dried over MgSO4
  6. filtrationfiltered
  7. customevaporated under reduced pressure before purification by column chromatography on SiO2
  8. washeluting with 2% EtOH in DCM

Sources & evidence

ORD record
ord-f5aac19b926e4bff89d99858dba55d89
Source dataset
uspto-grants-2015_02
Patent number
US08962665B2

Reaction notes

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