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

HRID 1921904ノート

反応式

HRID 1921904 の反応式
[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]

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 180Acetone溶媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-5180db99d776428e94f1ec8d03af9976
出典データセット
uspto-grants-2012_05
特許番号
US08173704B2

反応ノート

読み込み中…