Potassium Phosphate, Tribasic → Tert-butyl 4-[5-(4-fluorophenyl)pyrimidin-2-yl]piperazine-1-carboxylate

HRID 393701Notes

Reaction equation

HRID 393701 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:19]=[CH:18][C:17](Br)=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.O.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>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:19]=[CH:18][C:17]([C:25]3[CH:26]=[CH:27][C:22]([F:21])=[CH:23][CH:24]=3)=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2856454-Fluorophenylboronic acidHCID 21914476tert-Butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylate

Product 1

HCID 69850026Tert-butyl 4-[5-(4-fluorophenyl)pyrimidin-2-yl]piperazine-1-carboxylateYield 96%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

4-(5-Bromopyrimidin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (1.01 g), 4-fluorophenylboronic acid (0.45 g), tetrakis(triphenylphosphine)palladium(0) (0.12 g) and potassium phosphate (1.25 g) were dissolved in a mixture of 1,2-dimethoxyethane (40 ml) and water (10 ml), degassed and heated to reflux under nitrogen. After 16 h. the reaction was cooled, reduced in vacuo, dissolved in diethyl ether (100 ml) and washed with water (3×20 ml), saturated brine (20 ml), dried (Na2SO4) and evaporated. The black residue was then chromatographed on silica, with 2% methanol/dichloromethane to provide the title compound as a pale yellow solid (1.01 g, 96%).

Workup

  1. customdegassed
  2. temperatureheated
  3. temperatureto reflux under nitrogen
  4. temperatureAfter 16 h. the reaction was cooled
  5. dissolutiondissolved in diethyl ether (100 ml)
  6. washwashed with water (3×20 ml), saturated brine (20 ml)
  7. dry with materialdried (Na2SO4)
  8. customevaporated
  9. customThe black residue was then chromatographed on silica, with 2% methanol/dichloromethane

Sources & evidence

ORD record
ord-8ebf243a8c5e41ae92a29241eb146345
Source dataset
uspto-grants-2004_10
Patent number
US06809100B2

Reaction notes

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