Potassium Carbonate → 4-(3-Methyl-5-nitro-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1993652Notes

Reaction equation

HRID 1993652 reaction equation
Cl[C:2]1[C:7]([CH3:8])=[CH:6][C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1.[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].C([O-])([O-])=O.[K+].[K+].CCOC(C)=O.O>CN(C=O)C>[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][N:22]([C:2]2[C:7]([CH3:8])=[CH:6][C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=2)[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 896482-Chloro-3-methyl-5-nitropyridineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 22728543Water ethylacetate

Product 1

HCID 685370044-(3-Methyl-5-nitro-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl esterYield 85.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Treat a slurry of 2-chloro-3-methyl-5-nitro-pyridine (27.00 g, 0.156 mol) and piperazine-1-carboxylic acid tert-butyl ester (32.03 g, 0.172 mol) in anhydrous DMF (270 mL) with K2CO3 (34.55 g, 0.250 mol), then heat the reaction mixture at 80° C. under N2 overnight. Pour the resulting reaction mixture into 1/1 EtOAc/H2O (3,000 mL), separate the layers, then extract the aqueous layer with EtOAc (1,000 mL). Wash the combined organics with saturated aq. sodium chloride (3×1,000 mL each), dry over MgSO4, filter, then concentrate under reduced pressure to give a yellow solid. Slurry the yellow solid in hexanes/EtOAc, then recover the resulting solid by vacuum filtration. Wash with hexanes and vacuum filter to give (42.84 g) of 4-(3-methyl-5-nitro-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester as a yellow solid. Concentrate the filtrate under reduced pressure to give a yellow solid. Slurry the yellow solid in hexanes, then recover the resulting solid by vacuum filtration, washing with hexane and drying under vacuum filtration to give an additional (5.38 g) of 4-(3-methyl-5-nitro-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester compound as a yellow solid (48.22 g, 95.9% yield). 1H NMR (400 MHz, CDCl3) δ 8.96 (d, 1H), 8.14 (d, 1H), 3.57 (m, 4H), 3.41 (m, 4H), 2.36 (s, 3H), 1.48 (s, 9H); TOF-MS [ES+, M+H] Obs. m/z 323.1723, Calc. m/z 323.1719; Anal. Calcd. For C15H22N4O4: C, 55.88; H, 6.87; N, 17.37. Found C, 55.94; H, 6.87; N, 17.14.

Workup

  1. additionPour
  2. customseparate the layers
  3. extractionextract the aqueous layer with EtOAc (1,000 mL)
  4. washWash the combined organics with saturated aq. sodium chloride (3×1,000 mL each)
  5. dry with materialdry over MgSO4
  6. filtrationfilter
  7. concentrationconcentrate under reduced pressure
  8. customto give a yellow solid
  9. customrecover the resulting solid
  10. filtrationby vacuum filtration
  11. washWash with hexanes and vacuum
  12. filtrationfilter

Sources & evidence

ORD record
ord-c0b9b06d7fcc4e218d915df0e80a7947
Source dataset
uspto-grants-2010_01
Patent number
US07652015B2

Reaction notes

Loading…