Réaction #92243

Équation de réaction

2-(4-(Trifluoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

N-ethyl-N-isopropylpropan-2-amine

(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

→

title compound

Rendement 72.7%

(S)-methyl 2-(tert-butoxy)-2-(2-methyl-4-(4-(trifluoromethyl)phenyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-b]pyridin-3-yl)acetate

Rendement 72.7%

Solvants

ethyl acetate

water

dioxane

water

Conditions de réaction

Traitement

1. 1
   AutreThe reaction mixture was degassed with argon for 2 minutes
2. 2
   Autrethe vessel was sealed
3. 3
   TempératureThe reaction mixture was cooled to room temperature
4. 4
   AutreThe layers of the filtrate were separated
5. 5
   Lavagethe organic layer was washed with brine (30 mL)
6. 6
   Séchagedried (MgSO4)
7. 7
   Concentrationconcentrated in vacuo
8. 8
   Autreto yield the crude product as a brown gum
9. 9
   AutreThe residue was purified by flash column chromatography
10. 10
    Lavageeluting with ethyl acetate in heptane (10%)

Mode opératoire

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+].

Source