4-Bromo-2-chloropyridine → Isobutyl 4-(2-chloropyridin-4-yl)piperazine-1-carboxylate

HRID 2245230Notes

Reaction equation

HRID 2245230 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([Cl:8])[CH:3]=1.[N:9]1([C:15]([O:17][CH2:18][CH:19]([CH3:21])[CH3:20])=[O:16])[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.C(O[Na])(C)(C)C>C1(C)C=CC=CC=1.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].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>[Cl:8][C:4]1[CH:3]=[C:2]([N:12]2[CH2:11][CH2:10][N:9]([C:15]([O:17][CH2:18][CH:19]([CH3:21])[CH3:20])=[O:16])[CH2:14][CH2:13]2)[CH:7]=[CH:6][N:5]=1

Participants

8

Reactant 3

HCID 38477704-Bromo-2-chloropyridineHCID 11788701Isobutyl piperazine-1-carboxylateHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 58853192Isobutyl 4-(2-chloropyridin-4-yl)piperazine-1-carboxylateYield 63.1%

Reagents, catalysts & solvents 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

4-Bromo-2-chloropyridine (125 mg, 0.65 mmol), isobutyl piperazine-1-carboxylate (93 mg, 0.5 mmol), Pd2(dba)3 (10 mg, 10 μmol), t-BuONa (72 mg, 0.75 mmol), and Xantphos (17 mg, 30 μmol) in dry toluene (5 mL) were sealed in a microwave vessel and heated by microwave irradiation at 150° C. for 15 minutes. The reaction was diluted with EtOAc, washed with water, dried over Na2SO4, and evaporated under reduced pressure. Purification by flash chromatography (SiO2, MeOH/CH2Cl2) afforded 3a as a tan oil (94 mg, 63% yield). LCMS: m/z 298.5 (M+H)+ at 1.93 minutes (10%-99% CH3CN/H2O), (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA).

Workup

  1. washwashed with water
  2. dry with materialdried over Na2SO4
  3. customevaporated under reduced pressure
  4. customPurification by flash chromatography (SiO2, MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-167526362202448496cfb45ef8f4755c
Source dataset
uspto-grants-2010_03
Patent number
US07683065B2

Reaction notes

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