Potassium Iodide → 5-{(3,5-Difluoro-4-hydroxybenzyl)-[2-(5-fluoro-2-{[4'-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)ethyl]amino}pentanoic acid

HRID 1921904Notes

Reaction equation

HRID 1921904 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][CH:27]=3)=[CH:22][CH:21]=2)=[C:6]([CH2:8][CH2:9][NH:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16])[CH:7]=1.Br[CH2:37][C:38]1[CH:39]=[C:40]([F:56])[C:41]([O:45][Si](C(C)C)(C(C)C)C(C)C)=[C:42]([F:44])[CH:43]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CC(C)=O.C(OCC)(=O)C.O>[F:44][C:42]1[CH:43]=[C:38]([CH:39]=[C:40]([F:56])[C:41]=1[OH:45])[CH2:37][N:10]([CH2:9][CH2:8][C:6]1[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=1[O:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:27]=[CH:28][C:29]([C:32]([F:33])([F:34])[F:35])=[CH:30][CH:31]=2)=[CH:22][CH:21]=1)[CH2:11][CH2:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16]

Participants

8

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 579719075-{[2-(5-Fluoro-2-{[4'-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)ethyl]amino}pentanoic acidHCID 579719463,5-Difluoro-4-triisopropylsilanyloxybenzyl bromide

Product 1

HCID 162256195-{(3,5-Difluoro-4-hydroxybenzyl)-[2-(5-fluoro-2-{[4'-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)ethyl]amino}pentanoic acid

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 40 mg (0.08 mmol) of 5-{[2-(5-fluoro-2-{[4′-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)ethyl]amino}pentanoic acid in 5 ml of acetone is mixed with 54.5 mg (0.09 mmol) of [4-(bromomethyl)-2,6-difluorophenoxy]triisopropyl)silane (Example 16A), 22.6 mg (0.16 mmol) of potassium carbonate and 20.3 mg (0.12 mmol) of potassium iodide and heated under reflux for 12 h. Cooling is followed by addition of water to the mixture and extraction with ethyl acetate. The organic phase is washed with saturated sodium chloride solution, dried over magnesium sulfate and the solvent is distilled off in vacuo. The resulting residue is purified by preparative HPLC. 15.3 mg (0.024 mmol, 30% of theory) of the title compound are obtained.

Workup

  1. temperatureheated
  2. temperatureunder reflux for 12 h
  3. temperatureCooling
  4. washThe organic phase is washed with saturated sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. distillationthe solvent is distilled off in vacuo
  7. customThe resulting residue is purified by preparative HPLC

Sources & evidence

ORD record
ord-5180db99d776428e94f1ec8d03af9976
Source dataset
uspto-grants-2012_05
Patent number
US08173704B2

Reaction notes

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