Sodium Chloride → [2-(4-Methyl-piperazin-1-yl)-5-nitro-pyridin-4-yl]-acetic acid ethyl ester

HRID 1992651Notes

Reaction equation

HRID 1992651 reaction equation
P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH2:9]([O:11][C:12](=[O:24])[CH2:13][C:14]1[C:19]([N+:20]([O-:22])=[O:21])=[CH:18][N:17]=[C:16](Br)[CH:15]=1)[CH3:10].[CH3:25][N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.[Na+].[Cl-]>COCCOC.CCOC(C)=O.O.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.[Pd].C(P([C-]1C=CC=C1)C(C)(C)C)(C)(C)C.C1(C2[C-](C3C=CC=CC=3)C(C3C=CC=CC=3)=C(C3C=CC=CC=3)C=2C2C=CC=CC=2)C=CC=CC=1.[Fe+2]>[CH2:9]([O:11][C:12](=[O:24])[CH2:13][C:14]1[C:19]([N+:20]([O-:22])=[O:21])=[CH:18][N:17]=[C:16]([N:29]2[CH2:30][CH2:31][N:26]([CH3:25])[CH2:27][CH2:28]2)[CH:15]=1)[CH3:10]

Participants

10

Reactant 4

HCID 5234Sodium ChlorideHCID 531671-MethylpiperazineHCID 62657Potassium Phosphate, TribasicHCID 86623476Ethyl 2-(2-Bromo-5-nitro-4-pyridyl)acetate

Product 1

HCID 66869335[2-(4-Methyl-piperazin-1-yl)-5-nitro-pyridin-4-yl]-acetic acid ethyl ester

Reagents, catalysts & solvents 5

HCID 72499888Dibenzalacetone palladiumCatalystHCID 129828017Ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+);(2,3,4,5-tetraphenylcyclopenta-1,4-dien-1-yl)benzeneCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Potassium phosphate (2.48 g, 11.67 mmol) is dried at 120° C. under high vacuum for 45 minutes. After cooling to RT and venting with dry argon, palladium dibenzylideneacetone (Pd2(dba)3, 24 mg, 0.026 mmol) and di-tert-butylphosphino pentaphenylferrocene (37 mg, 0.052 mmol) are added. (2-Bromo-5-nitro-pyridin-4-yl)-acetic acid ethyl ester (750 mg, 2.59 mmol), dissolved in 1,2-dimethoxyethane (10 ml, dried by passing through a column of basic aluminium oxide), and 1-methyl piperazine (780 mg, 7.78 mmol) are added. The reaction mixture is stirred at RT for 10 minutes, after which TLC and MS analysis indicated complete conversion of the starting material. The reaction mixture is diluted with EtOAc and poured into a saturated solution of NaCl in water. The organic layer is separated, dried over Na2SO4, and the solvent is evaporated. Purification of the residue by FCC (hexane/EtOAc, gradient from 95:5 to 90:10) affords the title compound. 1H NMR (CDCl3, 400 MHz): δ 1.26 (t, J=7 Hz, 3H), 2.35 (s, 3H), 2.50 (m, 4H), 3.76 (m, 4H), 3.94 (s, 2H), 4.18 (q, J=7 Hz, 2H), 6.36 (s, 1H), 9.05 (s, 1H). ES+−MS: 309.3 [M+H]+, ES−−MS: 307.3 [M−H]−.

Workup

  1. customdried
  2. additionare added
  3. customThe organic layer is separated
  4. dry with materialdried over Na2SO4
  5. customthe solvent is evaporated
  6. customPurification of the residue by FCC (hexane/EtOAc, gradient from 95:5 to 90:10)

Sources & evidence

ORD record
ord-c6db34a28a55440e89ac1fd063c3d811
Source dataset
uspto-grants-2010_01
Patent number
US07648989B2

Reaction notes

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