Potassium Carbonate → 2-(2-(3-trifluoromethylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxy)-2-methylpropanoic acid

HRID 68619

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HRID 68619 반응식
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([C:9]2[CH:10]=[C:11]([CH:25]=[CH:26][C:27]=2[OH:28])[CH2:12][N:13]([CH3:24])[S:14]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[CH:6]=[CH:7][CH:8]=1.C([O:35][C:36](=[O:41])[C:37](Br)([CH3:39])[CH3:38])(C)(C)C.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[F:30][C:2]([F:1])([F:29])[C:3]1[CH:4]=[C:5]([C:9]2[CH:10]=[C:11]([CH2:12][N:13]([CH3:24])[S:14]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)(=[O:16])=[O:15])[CH:25]=[CH:26][C:27]=2[O:28][C:37]([CH3:39])([CH3:38])[C:36]([OH:41])=[O:35])[CH:6]=[CH:7][CH:8]=1

참가 물질

5

반응물 3

HCID 11430Potassium CarbonateHCID 90290tert-Butyl 2-bromo-2-methylpropionateHCID 66868277N-(3-(3-trifluoromethylphenyl)-4-hydroxybenzyl)-4-fluoro-N-methylbenzenesulfonamide

생성물 1

HCID 668690412-(2-(3-trifluoromethylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxy)-2-methylpropanoic acid수율 4.7%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
80 °C

실험 절차

To a solution of N-(3-(3-trifluoromethylphenyl)-4-hydroxybenzyl)-4-fluoro-N-methylbenzenesulfonamide (36) (50.0 mg, 0.114 mmol, 1 eq) in DMF (3 mL) under argon, was added t-butyl-2-bromo-2-methylpropanoate (66.0 mg, 0.296 mmol, 2.6 eq) and potassium carbonate (31 mg, 0.224 mmol, 2 eq). The mixture was stirred at 80° C. for 16 h, cooled to room temperature and partitioned with saturated sodium bicarbonate and EtOAc. The organic layer was separated, dried (Na2SO4), and concentrated in vacuo. The crude residue was dissolved in TFA/DCM (1 mL/1 mL) and stirred at room temperature for 1 h. Solvent was removed in vacuo and the residue was purified via reversed phase semi-preparative HPLC to afford 2.8 mg of 2-(2-(3-trifluoromethylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxy)-2-methylpropanoic acid (Example 34). 1HNMR (CD3OD, 400 MHz): δ 7.91 (m, 3H), 7.88 (m, 1H), 7.61 (m, 2H), 7.35 (t, 2H), 7.27 (d, 2H), 6.90 (d, 1H), 4.20 (s, 2H), 2.67 (s, 3H), 1.46 (s, 6H). MS (ESI): MH+=526.1. HPLC (Method B) tR=2.53 min.

후처리

  1. temperaturecooled to room temperature
  2. custompartitioned with saturated sodium bicarbonate and EtOAc
  3. customThe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. dissolutionThe crude residue was dissolved in TFA/DCM (1 mL/1 mL)
  7. stirringstirred at room temperature for 1 h
  8. customSolvent was removed in vacuo
  9. customthe residue was purified via reversed phase semi-preparative HPLC

출처 및 근거

ORD 기록
ord-9e7332b10565418e9fad2ae0cb3142bc
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822467B2

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