Water → HCID 23599496, compound

HRID 891453Notes

Reaction equation

HRID 891453 reaction equation
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([NH:9][C:10]([C:12]1[S:13][C:14](Br)=[CH:15][CH:16]=1)=[O:11])[CH2:2]2.[C:18](=[O:21])([O-])[O-].[K+].[K+].O>N1C=CC=CC=1.[Cu](I)I>[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([NH:9][C:10]([C:12]1[S:13][C:14]([O:21][C:18]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[CH:15][CH:16]=1)=[O:11])[CH2:2]2

Participants

6

Reactant 3

HCID 962WaterHCID 11430Potassium CarbonateHCID 9836523HCID 9836523, compound

Product 1

HCID 23599496HCID 23599496, compoundYield 34.7%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 1049PyridineSolvent

Conditions

Temperature
125 °C

Procedure

To a solution of (R)-N-(1-azabicyclo[2.2.2]oct-3-yl)(5-bromothiophene-2-carboxamide) (463 mg) in pyridine (10 mL) phenol (158 mg), copper iodide (32 mg) and potassium carbonate (97 mg) were added. The mixture was stirred at 125° C. for 65 h under nitrogen. Water was added and the aqueous layer was extracted with chloroform. Following evaporation, the residue was purified by flash chromatography using 5-20% 3.5M methanolic ammonia/chloroform mixtures as the eluent and then by reverse phase HPLC on a Waters Bondapak® C18 column using a gradient of acetonitrile and 0.1% aqueous trifluoroacetic acid as the eluent. The free base was prepared by basification of the product-containing fractions and extraction into chloroform followed by evaporation to gave the title compound (80 mg); MS (ES+) 329 (MH+).

Workup

  1. extractionthe aqueous layer was extracted with chloroform
  2. customevaporation
  3. customthe residue was purified by flash chromatography
  4. customThe free base was prepared by basification of the product-containing fractions and extraction into chloroform
  5. customfollowed by evaporation

Sources & evidence

ORD record
ord-b6bbfd82d89044459657937f09fcc4eb
Source dataset
uspto-grants-2006_02
Patent number
US07001914B2

Reaction notes

Loading…