Potassium Carbonate → HCID 66916938, compound

HRID 2075127Notes

Reaction equation

HRID 2075127 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[O:9])=[CH:4][CH:3]=1.[Cl:16][C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>C(O)(C)C.O.[Pd]>[ClH:16].[Cl:16][C:17]1[CH:22]=[C:21]([C:2]2[CH:7]=[CH:6][C:5]([C:8]([CH:10]3[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)=[O:9])=[CH:4][CH:3]=2)[CH:20]=[CH:19][CH:18]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 2734323(3-Chlorophenyl)boronic acidHCID 13180300(4-Bromophenyl)(piperidin-4-yl)methanone

Product 1

HCID 66916938HCID 66916938, compoundYield 90.6%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

A round bottom flask was charged with (4-bromophenyl)(piperidine-4-yl)methanone (20.0 g, 74.6 mmol), 3-chlorophenyl boronic acid (17.4 g, 111 mmol, 1.5 eq), and palladium encapsulated catalyst (Aldrich, Pd EnCat-TPP®, catalyst species PdCl2(PPh3)2) (5.2 g, 0.187 mmol, 0.05 eq). These solids were suspended in isopropanol (570 ml) and allowed to stir for five minutes. To the mixture was added potassium carbonate (30.8 g, 224 mmol, 3 eq) dissolved in H2O (30 ml). The reaction mixture was heated to 80° C. for 16 hours and deemed complete by LC/MS. The suspension was filtered through a small bed of Celite® and the filtrate was concentrated to dryness. The resulting solids were dissolved in isopropyl acetate (400 ml) and washed with water (3×75 ml). The organic layer was then cooled to 0° C. (ice/water bath) and to this stirring solution was added slowly 6 N HCl until solids crystallized. The solids were filtered and dried in a vacuum oven for 16 hours at 50° C. to afford 16.9 g of compound 2 (68% yield) in >98% HPLC purity. MH+=300, 302 (about 3:1). Palladium: 3 ppm.

Workup

  1. filtrationThe suspension was filtered through a small bed of Celite®
  2. concentrationthe filtrate was concentrated to dryness
  3. dissolutionThe resulting solids were dissolved in isopropyl acetate (400 ml)
  4. washwashed with water (3×75 ml)
  5. temperatureThe organic layer was then cooled to 0° C. (ice/water bath)
  6. additionto this stirring solution was added slowly 6 N HCl until solids
  7. customcrystallized
  8. filtrationThe solids were filtered
  9. customdried in a vacuum oven for 16 hours at 50° C.

Sources & evidence

ORD record
ord-b24d2ab1794a460382f196974ce5c0f3
Source dataset
uspto-grants-2011_04
Patent number
US07919618B2

Reaction notes

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