Hydrochloric Acid → N-(6-Chloro-4-formyl-3-pyridinyl)-2,2-dimethylpropanamide

HRID 2418125Notes

Reaction equation

HRID 2418125 reaction equation
[CH3:1][C:2]([CH3:14])([CH3:13])[C:3]([NH:5][C:6]1[CH:7]=[CH:8][C:9]([Cl:12])=[N:10][CH:11]=1)=[O:4].N#N.CO.C([Li])(C)(C)C.CN(C)[CH:26]=[O:27].Cl>C1COCC1.CCOCC.O>[CH3:1][C:2]([CH3:14])([CH3:13])[C:3]([NH:5][C:6]1[C:7]([CH:26]=[O:27])=[CH:8][C:9]([Cl:12])=[N:10][CH:11]=1)=[O:4]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 15592370HCID 15592370, compoundHCID 86597747HCID 86597747, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 15592371N-(6-Chloro-4-formyl-3-pyridinyl)-2,2-dimethylpropanamideYield 29.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A three-necked flask, equipped with a thermometer, a magnetic stirrer and a nitrogen inlet, was flushed with nitrogen. The flask was charged with 10.63 g of 2,2-dimethyl-N-(2-chloro-5-pyridinyl)propanamide (50 mmoles) and stoppered with a rubber septum. 100 Ml of THF was added to the flask. The flask was cooled in a liquid N2 /MeOH slush bath and 52.4 ml (110 mmoles) of 2.1M t-butyllithium was slowly added maintaining the temperature ≤75° C. by the rate of addition. The flask was transferred to a dry-ice/isopropanol (IPA) bath and stirred for 1.5 hours when a solution of 10.95 g (150 mmoles) of dimethylformamide in 5 ml of THF was added. The mixture was stirred at -78° C. for 30 minutes, 40 ml of 6N HCl was then added to the flask and the reaction mixture was allowed to warm to room temperature. After stirring for 30 minutes at room temperature, water and ether were added and the organic layer was separated. The aqueous layer was washed twice with ether and the combined organic layers washed with saturated NaCl, dried over MgSO4 and evaporated to leave an oil. The oil was triturated sequentially with water and ether and filtered to remove precipitated solids. The ethereal filtrate was recovered and dried over MgSO4 and the ether evaporated. Chromatography of the oil residue by preparative liquid chromatography (eluting with 20% EtOAc (ethyl acetate)/hexane) gave 3.5 g of the aldehyde (29 % of theoretical) as a pale yellow solid. The solid was recrystallized from hexane to give yellow needles having a melting point of 105°-106.5° C. Carbon, hydrogen, nitrogen and chlorine content calculated for C11H13ClN2O is C, 54.89; H, 5.44; N, 11.64 and Cl, 14.73 percent by weight which compares to that actually found upon analysis of C, 54.79; H, 5.38; N, 11.63; and Cl, 14.74.

Workup

  1. customA three-necked flask, equipped with a thermometer, a magnetic stirrer and a nitrogen inlet
  2. customwas flushed with nitrogen
  3. temperaturemaintaining the temperature ≤75° C.
  4. additionby the rate of addition
  5. customThe flask was transferred to a dry-ice/isopropanol (IPA) bath
  6. additionwas added
  7. temperatureto warm to room temperature
  8. stirringAfter stirring for 30 minutes at room temperature
  9. customthe organic layer was separated
  10. washThe aqueous layer was washed twice with ether
  11. washthe combined organic layers washed with saturated NaCl
  12. dry with materialdried over MgSO4
  13. customevaporated
  14. customto leave an oil
  15. customThe oil was triturated sequentially with water and ether
  16. filtrationfiltered
  17. customto remove
  18. customprecipitated solids
  19. customThe ethereal filtrate was recovered
  20. dry with materialdried over MgSO4
  21. customthe ether evaporated
  22. washChromatography of the oil residue by preparative liquid chromatography (eluting with 20% EtOAc (ethyl acetate)/hexane)

Sources & evidence

ORD record
ord-e3425c0c444846a4a57f779ddf97f3c1
Source dataset
uspto-grants-1984_09
Patent number
US04472193

Reaction notes

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