Potassium Carbonate → (R)-2-Ethyl-piperazine-1,4-dicarboxylic acid 4-tert-butyl ester 1-(2,6-difluoro-3-methyl-benzyl) ester

HRID 1794138Notes

Reaction equation

HRID 1794138 reaction equation
Br[C:2]1[C:3]([F:28])=[C:4]([C:24]([F:27])=[CH:25][CH:26]=1)[CH2:5][O:6][C:7]([N:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][C@H:10]1[CH2:22][CH3:23])=[O:8].[CH3:29]B1OB(C)OB(C)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:28][C:3]1[C:2]([CH3:29])=[CH:26][CH:25]=[C:24]([F:27])[C:4]=1[CH2:5][O:6][C:7]([N:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][C@H:10]1[CH2:22][CH3:23])=[O:8]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 69141503(R)-2-Ethyl-piperazine-1,4-dicarboxylic acid 4-tert-butyl ester 1-(3-bromo-2,6-difluoro-benzyl) ester

Product 1

HCID 69141585(R)-2-Ethyl-piperazine-1,4-dicarboxylic acid 4-tert-butyl ester 1-(2,6-difluoro-3-methyl-benzyl) esterYield 82.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of (R)-2-ethyl-piperazine-1,4-dicarboxylic acid 4-tert-butyl ester 1-(3-bromo-2,6-difluoro-benzyl) ester (226 mg), tetrakis(triphenylphosphine)palladium (56 mg), trimethylboroxine (122 mg) and potassium carbonate (200 mg) in dioxane (5 mL) was heated to reflux with stirring for 6 h. The cooled was mixture was partitioned between water and ethylacetate. The water phase was extracted once with ethylacetate, organic phases were pooled and dried with Na2SO4 to yield after evaporation a dark oil (259 mg). This residue was purified by column chromatography (silica gel; n-hexane/ethylacetate gradient) to yield 160 mg (82%) of a yellow oil. MS (ISP): 416.4 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureto reflux
  3. customwas partitioned between water and ethylacetate
  4. extractionThe water phase was extracted once with ethylacetate, organic phases
  5. dry with materialdried with Na2SO4
  6. customto yield
  7. customafter evaporation a dark oil (259 mg)
  8. customThis residue was purified by column chromatography (silica gel; n-hexane/ethylacetate gradient)

Sources & evidence

ORD record
ord-684b40d2732143c7b8ea438e08da94d9
Source dataset
uspto-grants-2006_04
Patent number
US07022707B2

Reaction notes

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