Cesium carbonate → 4-(6-Nitropyridin-3-yl)-3-oxopiperazine-1-carboxylic acid tert-butyl ester

HRID 1853244Notes

Reaction equation

HRID 1853244 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([N+:8]([O-:10])=[O:9])=[N:6][CH:7]=1.[C:11]([N:18]1[CH2:23][CH2:22][NH:21][C:20](=[O:24])[CH2:19]1)([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[C:14]([O:13][C:11]([N:18]1[CH2:23][CH2:22][N:21]([C:2]2[CH:7]=[N:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)[C:20](=[O:24])[CH2:19]1)=[O:12])([CH3:17])([CH3:15])[CH3:16]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 8176205-Bromo-2-nitropyridineHCID 3157178Tert-butyl 3-oxopiperazine-1-carboxylate

Product 1

HCID 592909524-(6-Nitropyridin-3-yl)-3-oxopiperazine-1-carboxylic acid tert-butyl esterYield 77%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 5-bromo-2-nitropyridine (200 mg, 1 mmol), 1-Boc-3-oxopiperazine (240 mg, 1.2 mmol), Xantphos (43 mg, 0.075 mmol), cesium carbonate (326 mg, 1 mmol), palladium(II) acetate (11 mg, 0.049 mmol) in dioxane (5.5 mL) is heated to 120° C. in a Personal Chemistry microwave apparatus for 0.5 h. TLC and LCMS analysis indicates completion of the reaction. The reaction mixture is filtered through Celite, evaporated in vacuo, and the residue is partitioned between water and ethyl acetate. The organic layer is washed with brine, dried (Na2SO4) and evaporated in vacuo. Purification by flash chromatography on silica (ethyl acetate) provides 4-(6-Nitropyridin-3-yl)-3-oxopiperazine-1-carboxylic acid tert-butyl ester as a pale brown solid (248 mg, 77%). MS (ESI) m/z 323 [M+H+].

Workup

  1. customcompletion of the reaction
  2. filtrationThe reaction mixture is filtered through Celite
  3. customevaporated in vacuo
  4. customthe residue is partitioned between water and ethyl acetate
  5. washThe organic layer is washed with brine
  6. dry with materialdried (Na2SO4)
  7. customevaporated in vacuo
  8. customPurification by flash chromatography on silica (ethyl acetate)

Sources & evidence

ORD record
ord-d3d6ec3e37d54f3e85aab180337ca40c
Source dataset
uspto-grants-2015_02
Patent number
US08962630B2

Reaction notes

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