Cesium carbonate → Tert-butyl 1'-(6-chloropyrazin-2-yl)-4,4'-bipiperidine-1-carboxylate

HRID 1947663Notes

Reaction equation

HRID 1947663 reaction equation
[N:1]1([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:6][CH2:5][CH:4]([CH:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH2:3][CH2:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:26][C:27]1[CH:32]=[N:31][CH:30]=[C:29](Cl)[N:28]=1>CN1C(=O)CCC1.C(=O)(O)[O-].[Na+]>[Cl:26][C:27]1[N:28]=[C:29]([N:10]2[CH2:11][CH2:12][CH:7]([CH:4]3[CH2:5][CH2:6][N:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:2][CH2:3]3)[CH2:8][CH2:9]2)[CH:30]=[N:31][CH:32]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 785042,6-DichloropyrazineHCID 117475994,4'-Bipiperidine, 1-boc protected

Product 1

HCID 59178885Tert-butyl 1'-(6-chloropyrazin-2-yl)-4,4'-bipiperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 13387N-methyl-2-pyrrolidoneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

The tert-butyl 4,4′-bipiperidine-1-carboxylate (100 mg, 0.45 mmol) and cesium carbonate (364 mg, 1.1 mmol) were slurried in NMP (0.75 ml) and the 2,6-dichloropyrazine (67 mg, 0.45 mmol) added. The mixture was stirred at 70 C overnight. The slurry was diluted with 15% saturated sodium bicarbonate:water (40 ml) and extracted with DCM (3×25 ml). The combined organic fraction was washed with 4:1 water:saturated sodium bicarbonate (2×), brine, dried over magnesium sulfate, filtered, and the volatiles removed in vac. The crude material was purified by chromatography on silica gel with 20% acetone:hexanes to yield the title compound.

Workup

  1. extractionwater (40 ml) and extracted with DCM (3×25 ml)
  2. washThe combined organic fraction was washed with 4:1 water
  3. dry with materialsaturated sodium bicarbonate (2×), brine, dried over magnesium sulfate
  4. filtrationfiltered
  5. customthe volatiles removed in vac
  6. customThe crude material was purified by chromatography on silica gel with 20% acetone

Sources & evidence

ORD record
ord-b0df3e84ff6d4070a36c263635eff896
Source dataset
uspto-grants-2013_03
Patent number
US08399485B2

Reaction notes

Loading…