反応 #92243

ord-4ae5393f86f44a7db45e1eac58835424

反応条件

温度
100°CELSIUS
詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    その他The reaction mixture was degassed with argon for 2 minutes
  2. 2
    その他the vessel was sealed
  3. 3
    温度The reaction mixture was cooled to room temperature
  4. 4
    その他The layers of the filtrate were separated
  5. 5
    洗浄the organic layer was washed with brine (30 mL)
  6. 6
    乾燥dried (MgSO4)
  7. 7
    濃縮concentrated in vacuo
  8. 8
    その他to yield the crude product as a brown gum
  9. 9
    その他The residue was purified by flash column chromatography
  10. 10
    洗浄eluting with ethyl acetate in heptane (10%)

実験手順

2-(4-(Trifluoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (115 g, 0.42 mmol), N-ethyl-N-isopropylpropan-2-amine (120 μL, 0.64 mmol) and water (500 μL) were added to a stirred solution of (S)-methyl 2-(tert-butoxy)-2-(4-iodo-2-methyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-b]pyridin-3-yl)acetate (100 mg, 0.21 mmol) in dioxane (2 mL) in a reaction tube. The reaction mixture was degassed with argon for 2 minutes, then tetrakis(triphenylphosphine)palladium(0) (25 mg, 21 μmol) was added and the vessel was sealed and heated at 100° C. for 16 hours. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (30 mL) and water (30 mL) and the mixture was passed through a pad of celite. The layers of the filtrate were separated and the organic layer was washed with brine (30 mL), dried (MgSO4) and concentrated in vacuo to yield the crude product as a brown gum. The residue was purified by flash column chromatography eluting with ethyl acetate in heptane (10%) to give the title compound (75 mg, 72%) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ=0.96 (s, 9H), 1.85-1.35 (m, 6H), 2.72 (s, 3H), 2.85-2.75 (m, 2H), 3.69 (s, 3H), 4.91 (s, 1H), 7.40 (d, 1H), 7.61 (d, 1H), 7.71 (m, 2H). LCMS (run time=5 minutes, basic): Rt=3.64 minutes; m/z 492.06 [M+H+].

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US09447116B2uspto-grants-2016_09