4-Toluenesulfonyl chloride → HCID 10945567, compound

HRID 636552Notes

Reaction equation

HRID 636552 reaction equation
Cl/C(=C\C)/[C:3]#[N:4].[C:7]1(C)C=CC(S(Cl)(=O)=O)=C[CH:8]=1.[Na].[Cl:19][C:20]1[N:36]=[CH:35][CH:34]=[CH:33][C:21]=1[C:22]([N:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH:25]1[C:30](O)=O)=O>ClCCCl.C(N(CC)CC)C>[CH3:7][C:8]1[C:30]([C:3]#[N:4])=[C:25]2[N:24]([C:22]=1[C:21]1[C:20]([Cl:19])=[N:36][CH:35]=[CH:34][CH:33]=1)[CH2:29][CH2:28][CH2:27][CH2:26]2

Participants

7

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 5360545SodiumHCID 11065466HCID 11065466, compoundHCID 86756453HCID 86756453, compound

Product 1

HCID 10945567HCID 10945567, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
35 °C

Procedure

3.75 g of 2-chlorocrotononitrile are added to a solution of 5.16 g of para-toluenesulphonyl chloride in 120 cm3 of 1,2-dichloroethane. The solution obtained is clear. 4 g of the sodium salt of N-(2-chloronicotinoyl)piperidine-2-carboxylic acid are added with stirring. The addition causes a rise in temperature from 20° C. to 28° C. and the mixture is kept stirred for one hour at ambient temperature. 3.8 cm3 of triethylamine are then added dropwise and the temperature increases to 35° C. The solution is heated to 40° C. for one hour and 30 minutes. After cooling, the reaction mixture is concentrated at reduced pressure (2.7 kPa) at a temperature close to 60° C. A mixture of products is thus obtained which is chromatographed on a column of 1.8 cm diameter containing 90 g of silica (0.04-0.0063). Elution is carried out with chloroform at a pressure of 1.5 bar, 20-cm3 fractions being collected. The homogeneous fractions are combined and concentrated at reduced pressure (2.7 kPa) at a temperature close to 60° C. 2.81 g of 2-methyl-3-(2-chloro-3-pyridyl)-5,6,7,8-tetrahydroindolizine-1-carbonitrile are thus obtained in the form of cream crystals melting at about 134° C.

Workup

  1. customThe solution obtained
  2. additionThe addition
  3. customfrom 20° C. to 28° C.
  4. stirringthe mixture is kept stirred for one hour at ambient temperature
  5. temperatureThe solution is heated to 40° C. for one hour and 30 minutes
  6. temperatureAfter cooling
  7. concentrationthe reaction mixture is concentrated at reduced pressure (2.7 kPa) at a temperature
  8. customclose to 60° C
  9. additionA mixture of products
  10. customis thus obtained which
  11. customis chromatographed on a column of 1.8 cm diameter
  12. additioncontaining 90 g of silica (0.04-0.0063)
  13. washElution
  14. custombeing collected
  15. concentrationconcentrated at reduced pressure (2.7 kPa) at a temperature
  16. customclose to 60° C

Sources & evidence

ORD record
ord-5eb6318e2b154d658cbed72f4946dfbb
Source dataset
uspto-grants-2001_02
Patent number
US06194426B1

Reaction notes

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