Cesium fluoride → [2-{[3-(Propylsulfonyl)phenyl]ethynyl}-4-(3-thienyl)phenoxy]acetic acid

HRID 2390368노트

반응식

HRID 2390368 반응식
C([O:5][C:6](=[O:30])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12](Br)=[CH:11][C:10]=1[C:16]#[C:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([S:24]([CH2:27][CH2:28][CH3:29])(=[O:26])=[O:25])[CH:19]=1)(C)(C)C.[S:31]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32]1.[F-].[Cs+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:27]([S:24]([C:20]1[CH:19]=[C:18]([C:17]#[C:16][C:10]2[CH:11]=[C:12]([C:33]3[CH:34]=[CH:35][S:31][CH:32]=3)[CH:13]=[CH:14][C:9]=2[O:8][CH2:7][C:6]([OH:5])=[O:30])[CH:23]=[CH:22][CH:21]=1)(=[O:25])=[O:26])[CH2:28][CH3:29]

참가 물질

5

반응물 3

HCID 25953Cesium fluorideHCID 581760Thiophene-3-boronic acidHCID 56593972Tert-butyl(4-bromo-2-{[3-(propylsulfonyl)phenyl]ethynyl}phenoxy)acetate2회

생성물 1

HCID 46865088[2-{[3-(Propylsulfonyl)phenyl]ethynyl}-4-(3-thienyl)phenoxy]acetic acid

시약·촉매·용매 1

HCID 178418476HCID 178418476, 화합물촉매

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온도
150 °C

실험 절차

A mixture of tert-butyl (4-bromo-2-{[3-(propylsulfonyl)phenyl]ethynyl}phenoxy)acetate (Intermediate 191, 200 mg; 0.41 mmol), 3-thienylboronic acid (78 mg; 0.61 mmol), caesium fluoride (185 mg; 1.22 mmol) and bis(triphenylphosphine)palladium(II) chloride (28 mg; 0.04 mmol) was placed in a microwave tube. The tube was sealed and degased with nitrogen before adding dioxane (4 ml) and water (2 ml). The reaction mixture was heated at 150° C. for 15 minutes in a microwave reaction system. The reaction mixture was taken up in EtOAc and washed with water and brine. The organic phase was dried over MgSO4, filtered and concentrated. The residue was dissolved in DCM (1.00 ml), treated with a 4 N solution of HCl in dioxane (2.0 ml) and stirred for 1 day. The solvents were removed under reduced pressure and the residue purified by preparative HPLC to give the title compound as a white solid.

후처리

  1. customwas placed in a microwave tube
  2. customThe tube was sealed
  3. customdegased with nitrogen
  4. additionbefore adding dioxane (4 ml) and water (2 ml)
  5. washwashed with water and brine
  6. dry with materialThe organic phase was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionThe residue was dissolved in DCM (1.00 ml)
  10. additiontreated with a 4 N solution of HCl in dioxane (2.0 ml)
  11. customThe solvents were removed under reduced pressure
  12. customthe residue purified by preparative HPLC

출처 및 근거

ORD 기록
ord-23ed4abd4256464aa7d4c316b1d0824c
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08273769B2

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