Potassium Carbonate → HCID 178516210, compound

HRID 1984038Notes

Reaction equation

HRID 1984038 reaction equation
I[C:2]1[CH:26]=[CH:25][C:5]([O:6][CH:7]2[CH2:12][CH2:11][CH:10]([C:13]([N:15]3[CH2:20][CH2:19][N:18]([CH:21]4[CH2:24][CH2:23][CH2:22]4)[CH2:17][CH2:16]3)=[O:14])[CH2:9][CH2:8]2)=[CH:4][CH:3]=1.[NH:27]1[CH2:32][CH2:31][CH2:30]C[C:28]1=[O:33].C(=O)([O-])[O-].[K+].[K+]>CCOC(C)=O.[Cu]>[CH:21]1([N:18]2[CH2:19][CH2:20][N:15]([C:13]([C@H:10]3[CH2:11][CH2:12][C@H:7]([O:6][C:5]4[CH:25]=[CH:26][C:2]([N:27]5[CH2:32][CH2:31][CH2:30][C:28]5=[O:33])=[CH:3][CH:4]=4)[CH2:8][CH2:9]3)=[O:14])[CH2:16][CH2:17]2)[CH2:24][CH2:23][CH2:22]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 126652-PiperidoneHCID 68445216HCID 68445216, compound

Product 1

HCID 178516210HCID 178516210, compoundYield 52%

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 0.87 g (3.27 mmol) of cis-(4-cyclobutyl-piperazin-1-yl)-(4-hydroxy-cyclohexyl)-methanone, 0.80 g (3.64 mmol) of 4-iodephenol, 1.05 g (4.00 mmol) of triphenylphisphine in 20 ml THF, 0.92 g (4.00 mmol) of di-tert-butyl azodicarboxylate was added at 0° C., and stirred for 12 h at room temperature. After evaporation, the residue was purified by column chromatography on silica gel eluting with cyclohexane and ethyl acetate=from 100:0 to 2:1. The combined product fractions were evaporated to dryness to yield 0.54 g (21% yields, about 65% purity) of [4-(4-iodo-phenoxy)-cyclohexyl]-(4-cyclobutyl-piperazin-1-yl)-methanone. A mixture 100 mg of [4-(4-iodo-phenoxy)-cyclohexyl]-(4-cyclobutyl-piperazin-1-yl)-methanone, 142 mg (1.67 mmol) of 2-piperidone, 77 mg (0.56 mmol) of potassium carbonate and 37 mg (1.12 mmol) of copper was stirred at 175 degree for 6 hr. The mixture was diluted with AcOEt, filtered through celite. The filtrate was evaporated. The mixture was purified with preparative HPLC (CH3CN: 0.05% HCOOH-water, Zorbax Comb Ht 20*50 mm, 5 micron). The combined product fractions were evaporated. The residue was solved with saturated NaHCO3, extracted with AcOEt, washed with brine, dried over MgSO4, and evaporated to dryness to yield 31 mg (52%) of the title compound. MS (m/e): 426.2 (MH+).

Workup

  1. filtrationfiltered through celite
  2. customThe filtrate was evaporated
  3. customThe mixture was purified with preparative HPLC (CH3CN: 0.05% HCOOH-water, Zorbax Comb Ht 20*50 mm, 5 micron)
  4. customThe combined product fractions were evaporated
  5. extractionextracted with AcOEt
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-e1886001779b4c83b679bdd4957c31c4
Source dataset
uspto-grants-2009_06
Patent number
US07544683B2

Reaction notes

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