Ethanol → HCID 86647047, compound

HRID 1811796Notes

Reaction equation

HRID 1811796 reaction equation
[CH3:1][S:2]([N:5]1[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1)(=[O:4])=[O:3].[Cl:11][C:12]1[C:13]([Cl:20])=[N:14][CH:15]=[C:16]([CH:19]=1)[CH:17]=O.CCO.C([BH3-])#N.[Na+]>CC(O)=O>[Cl:11][C:12]1[CH:19]=[C:16]([CH2:17][N:8]2[CH2:9][CH2:10][N:5]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:6][CH2:7]2)[CH:15]=[N:14][C:13]=1[Cl:20]

Participants

6

Reactant 4

HCID 702EthanolHCID 7091611-(Methylsulfonyl)piperazineHCID 5003444Sodium cyanoborohydrideHCID 115356545,6-Dichloropyridine-3-carbaldehyde

Product 1

HCID 86647047HCID 86647047, compoundYield 52.6%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidCatalyst

Procedure

1-methanesulfonylpiperazine (1.1 g, 6.8 mmol) followed by a catalytic amount of AcOH (0.020 mL, 0.34 mmol) were added to a stirred solution of 5,6-dichloronicotinaldehyde (1.20 g, 6.8 mmol) in EtOH (100 mL, 1713 mmol), the mixture was stirred at room temperature for 1 h (white precipitate formed), and the resulting suspension was treated portionwise with sodium cyanoborohydride (0.43 g, 6.8 mmol) (slightly exothermic) and stirred for another 2 h. The mixture was concentrated and quenched with 1 N HCl (aq), water (10 mL each) and EtOAc (50 mL). The separated aqueous layer was extracted with ethyl acetate (2×50 mL) and the combined organic layers were washed with brine, dried over Na2SO4, and concentrated to give a crude residue which was purified with flash column chromatography (ISCO Combiflash system, pure DCM to 3% 2 M NH3/MeOH in DCM) to give 1-((5,6-dichloropyridin-3-yl)methyl)-4-(methylsulfonyl)piperazine (1.16 g, 52%) as a white solid. LCMS (API-ES) m/z 325 (M+H)+; 1H NMR (400 MHz, CDCl3) δ 8.23 (s, 1H) 7.78 (s, 1H) 3.54 (s, 2H) 3.26 (br. s., 4H) 2.80 (s, 3H) 2.57 (br. s., 4H).

Workup

  1. custom(white precipitate formed)
  2. stirringstirred for another 2 h
  3. concentrationThe mixture was concentrated
  4. customquenched with 1 N HCl (aq), water (10 mL each) and EtOAc (50 mL)
  5. extractionThe separated aqueous layer was extracted with ethyl acetate (2×50 mL)
  6. washthe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customto give a crude residue which
  10. customwas purified with flash column chromatography (ISCO Combiflash system, pure DCM to 3% 2 M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-f2a7b6b74da04b48ae7b98fd69c9ee1a
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

Loading…