Pivalic acid → (E)-tert-butyl 3-(4-((6-methoxy-2-(4-(trifluoromethyl)phenyl)benzo[b]thiophen-3 yl)oxy)phenyl)acrylate

HRID 632629노트

반응식

HRID 632629 반응식
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:10]([O:11][C:12]3[CH:17]=[CH:16][C:15](/[CH:18]=[CH:19]/[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[CH:14][CH:13]=3)=[CH:9][S:8][C:7]=2[CH:27]=1.Br[C:29]1[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][CH:30]=1.CC(C)(C)C(O)=O.C(=O)([O-])[O-].[K+].[K+]>CC(N(C)C)=O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:10]([O:11][C:12]3[CH:17]=[CH:16][C:15](/[CH:18]=[CH:19]/[C:20]([O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])=[CH:14][CH:13]=3)=[C:9]([C:29]3[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][CH:30]=3)[S:8][C:7]=2[CH:27]=1

참가 물질

6

반응물 4

HCID 6417Pivalic acidHCID 11430Potassium CarbonateHCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 86730640(E)-tert-butyl 3-(4-((6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylate

생성물 1

HCID 86730641(E)-tert-butyl 3-(4-((6-methoxy-2-(4-(trifluoromethyl)phenyl)benzo[b]thiophen-3 yl)oxy)phenyl)acrylate수율 86%

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

실험 절차

To a 5 mL microwave vial, added a solution of (E)-tert-butyl 3-(4-((6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylate (50 mg, 0.13 mmol) in anhydrous DMA (1.5 mL), followed by 1-bromo-4-(trifluoromethyl)benzene (35.3 mg, 0.16 mmol), chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′,4′,6′-tri-i-propyl-1,1′-biphenyl][2-(2-aminoethyl)phenyl]palladium(II) (BrettPhos palladacycle 1st generation, 10.4 mg, 0.013 mmol), trimethylacetic acid (40.1 mg, 0.392 mmol) and potassium carbonate (54.2 mg, 0.392 mmol). The microwave vial was scaled, purged and back-filled with nitrogen. The reaction mixture subjected to microwave irradiation for 2 h at 150° C. Upon completion the reaction was diluted with EtOAc, and washed with water and brine. The combined organic layer was dried over anhydrous MgSO4, filtered and concentrated in vacuo to give a red brown residue which was purified by column chromatography (SiO2, 0-30% EtOAc/heptane) to afford (E)-tert-butyl 3-(4-((6-methoxy-2-(4-(trifluoromethyl)phenyl)benzo[b]thiophen-3 yl)oxy)phenyl)acrylate (59.4 mg, 0.11 mmol, 86% yield). 1H NMR (400 MHz, CD3OD) δ ppm=1.42-1.61 (m, 9 H), 3.77-3.98 (m, 3 H), 6.31 (d, J=15.66 Hz, 1 H), 6.87-7.04 (m, 3 H), 7.28 (d, J=9.09 Hz, 1 H), 7.46 (d, J=2.53 Hz, 1 H), 7.47-7.57 (m, 3 H), 7.65 (d, J=8.08 Hz, 2 H), 7.89 (d, J=8.08 Hz, 2 H), LC/MS (m/z, MH+): 471.40.

후처리

  1. custompurged
  2. additionback-filled with nitrogen
  3. customirradiation for 2 h at 150° C
  4. additionUpon completion the reaction was diluted with EtOAc
  5. washwashed with water and brine
  6. dry with materialThe combined organic layer was dried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a red brown residue which
  10. customwas purified by column chromatography (SiO2, 0-30% EtOAc/heptane)

출처 및 근거

ORD 기록
ord-7def578f646f478795049c1c16c41766
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09321746B2

반응 노트

불러오는 중…