Nitrogen → HCID 23289892, compound

HRID 366776Notes

Reaction equation

HRID 366776 reaction equation
N#N.Cl[CH:4]1[CH2:9][CH2:8][N:7]([CH3:10])[CH2:6][CH2:5]1.[Cl:11][C:12]1[CH:13]=[C:14]([S:18][CH2:19][C:20]2[C:21]([C:26](N(OC)C)=[O:27])=[N:22][CH:23]=[CH:24][CH:25]=2)[CH:15]=[CH:16][CH:17]=1.CCOC(C)=O>C1COCC1>[Cl:11][C:12]1[CH:13]=[C:14]([S:18][CH2:19][C:20]2[C:21]([C:26]([CH:4]3[CH2:9][CH2:8][N:7]([CH3:10])[CH2:6][CH2:5]3)=[O:27])=[N:22][CH:23]=[CH:24][CH:25]=2)[CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 947NitrogenHCID 8857Ethyl AcetateHCID 793424-chloro-N-methylpiperidineHCID 23289877HCID 23289877, compound

Product 1

HCID 23289892HCID 23289892, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

Anhydrous CeCl3 (1.1 g, 4.46 mmol) was placed in a 50 ml 2-necked flask and flamed out under vacuum. The vacuum was replaced with N2, and dry THF (20 ml) was added. The CeCl3/THF solution was stirred at room temperature for 16 hours and then cooled to -40° C., and the Mg-Grignard reagent from 4-chloro-1-methyl-piperidine (3 ml of an 0.8M stock solution in THF) was added. The resulting solution was stirred at -40° C. for 75 minutes, and then 3-[(3-chlorophenyl)thiomethyl]-N-methoxy-N-methyl-2-pyridinecarboxamide (345 mg, 1.07 mmol) was added dropwise. After 40 minutes, the mixture was poured into 5% HCI/EtOAc, stirred for 5 minutes, and then basified to pH ~8. The organic product was extracted with EtOAc (6×100 ml), the extracts were washed with brine, dried (Na2SO4), filtered and concentrated. The product was chromatographed on silica and eluted with 5-10%MeOH/CH2Cl2 to afford [3-[(3-chlorophenyl)thiomethyl]-2-pyridinyl][1-methyl-4-piperidinyl]methanone (251 mg, 64%); HRMS, FAB, calcd. 361.1141; found. 361.1141.

Workup

  1. temperatureflamed out under vacuum
  2. additionwas added
  3. waitAfter 40 minutes
  4. stirringstirred for 5 minutes
  5. extractionThe organic product was extracted with EtOAc (6×100 ml)
  6. washthe extracts were washed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe product was chromatographed on silica
  11. washeluted with 5-10%MeOH/CH2Cl2

Sources & evidence

ORD record
ord-7c3729ce8bef434b82525773f525b7c8
Source dataset
uspto-grants-2000_10
Patent number
US06130229

Reaction notes

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