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

HRID 1921904노트

반응식

HRID 1921904 반응식
[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]

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 180Acetone용매HCID 962Water용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-5180db99d776428e94f1ec8d03af9976
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08173704B2

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