Hydrochloric Acid → tert-butyl N-(6-chloro-3-formylpyridin-2-yl)carbamate

HRID 2171527Notes

Reaction equation

HRID 2171527 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH:5]=[CH:4][CH:3]=1.CN(C)CCN(C)C.C([Li])CCC.CN([CH:32]=[O:33])C.Cl>C(OCC)(=O)C.C1COCC1>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13])[C:5]([CH:32]=[O:33])=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 11253185tert-butyl N-(6-chloropyridin-2-yl)carbamateHCID 178418339Butyllithium

Product 1

HCID 51051664tert-butyl N-(6-chloro-3-formylpyridin-2-yl)carbamate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

The reaction takes place under argon, the apparatus is heat-dried and operated with a KPG stirrer. 15 g (65.6 mmol) of tert-butyl (6-chloropyridin-2-yl)carbamate (Example 25A) and 19 g (164 mmol) of 1,2-bis(dimethylamino)ethane are introduced into 270 ml of THF and cooled to −78° C. 102.5 ml (164 mmol) of butyllithium (1.6N) are added dropwise. After the dropwise addition is complete, the reaction is slowly warmed to −10° C. and kept at −10° C. for 2 h and then cooled again to −78° C., and 10 ml (131 mmol) of DMF are added. The reaction is slowly warmed to RT, and the reaction mixture is added to 1 l of ethyl acetate and 350 ml of 1N hydrochloric acid and stirred for 15 min, and the organic phase is separated off. It is washed with water and saturated sodium bicarbonate solution, dried over magnesium sulphate and concentrated in a rotary evaporator. The residue is mixed with diethyl ether and the solid is filtered off with suction and dried. 12.3 g (73% of theory) of the product are obtained as a solid.

Workup

  1. customthe apparatus is heat-dried
  2. additionAfter the dropwise addition
  3. temperaturethe reaction is slowly warmed to −10° C.
  4. temperaturecooled again to −78° C.
  5. temperatureThe reaction is slowly warmed to RT
  6. customthe organic phase is separated off
  7. washIt is washed with water and saturated sodium bicarbonate solution
  8. dry with materialdried over magnesium sulphate
  9. concentrationconcentrated in a rotary evaporator
  10. additionThe residue is mixed with diethyl ether
  11. filtrationthe solid is filtered off with suction
  12. customdried
  13. custom12.3 g (73% of theory) of the product are obtained as a solid

Sources & evidence

ORD record
ord-2c3cfeafd1fb4351bef24139a83df711
Source dataset
uspto-grants-2015_06
Patent number
US09051323B2

Reaction notes

Loading…