Trifluoroacetic acid → (+,-) Trans Propane-2-sulfonic acid {2-[4'-(2-methanesulfonylamino-ethyl)-biphenyl-4-yl]-cyclopentyl}-amide

HRID 989489Notes

Reaction equation

HRID 989489 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:12][CH2:11][CH2:10][C@H:9]2[NH:13][S:14]([CH:17]([CH3:19])[CH3:18])(=[O:16])=[O:15])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[C:26](O)([C:28](F)(F)F)=O>C(O)CC.O.C(Cl)Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:17][S:14]([NH:13][CH2:9][CH2:8][C:26]1[CH:28]=[CH:7][C:2]([C:2]2[CH:7]=[CH:6][C:5]([C@@H:8]3[CH2:12][CH2:11][CH2:10][C@H:9]3[NH:13][S:14]([CH:17]([CH3:19])[CH3:18])(=[O:16])=[O:15])=[CH:4][CH:3]=2)=[CH:3][CH:4]=1)(=[O:16])=[O:15]

Participants

8

Reactant 3

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 11784171(+,-) Trans Propane-2-sulfonic Acid [2-(4-iodo-phenyl)-cyclopentyl]-amide

Product 1

HCID 69112912(+,-) Trans Propane-2-sulfonic acid {2-[4'-(2-methanesulfonylamino-ethyl)-biphenyl-4-yl]-cyclopentyl}-amideYield 64%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 10311-PropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

(+,−) Trans propane-2-sulfonic acid [2-(4-iodo-phenyl)-cyclopentyl]-amide (300 mg, 0.76 mmol, prepared in example 2) and N-carbamic acid tert-butyl ester-N-methanesulfonamide-N-phenethyl-4-boronic acid (316 mg, 0.92 mmol) were dissolved in 20 mL of n-propanol and 25 mg (0.18 mmol)of potassium carbonate in 5 mL of water added. A catalytic amount of palladium acetate is added (9 mg) and the mixture refluxed at 90° C. for 4 hours. The reaction is worked up as in preparation 6. Dissolved the residue in methylene chloride and added 5 mL neat TFA and stirred overnight at room temperature. The TLC indicated the Boc protecting group had been removed and the reaction was concentrated in vacuo. Purification by silica chromatography using a Chromatotron® was achieved eluting with 95:5 methylene chloride:ethyl acetate to afford 225 mg (64%) of the title compound. The NMR was consistent with the assigned structure.

Workup

  1. customThe reaction is worked up as in preparation 6
  2. customhad been removed
  3. concentrationthe reaction was concentrated in vacuo
  4. customPurification by silica chromatography
  5. washwas achieved eluting with 95:5 methylene chloride

Sources & evidence

ORD record
ord-9f51b83e53374111a05950b2a75b36ef
Source dataset
uspto-grants-2003_10
Patent number
US06639107B1

Reaction notes

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