반응 #1110370

반응 방정식

5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

ethyl acrylate

tri-o-tolylphosphine

→

(E)-ethyl 3-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)acrylate

수율 86.0%

용매

ACN

반응 조건

후처리

1. 1
   기타The reaction mixture was purged with nitrogen
2. 2
   기타The solvent was removed under vacuum
3. 3
   workup.DISSOLUTIONThe residue was dissolved in ethyl acetate (15 mL)
4. 4
   세척washed with water (10 mL), brine (10 mL)
5. 5
   건조dried over sodium sulfate
6. 6
   농축The organic layer was concentrated under vacuum
7. 7
   기타the crude product was purified by flash chromatography on silica gel

실험 절차

To a solution of 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (0.85 g, 3.02 mmol) in ACN (20 mL), ethyl acrylate (0.605 g, 6.05 mmol), tri-o-tolylphosphine (0.368 g, 1.209 mmol), and TEA (1.204 ml, 9.07 mmol) were added. The reaction mixture was purged with nitrogen and then Pd2(dba)3 CHCl3 adduct (0.313 g, 0.302 mmol) was added. The reaction was heated at 90° C. overnight. The solvent was removed under vacuum. The residue was dissolved in ethyl acetate (15 mL), washed with water (10 mL), brine (10 mL), and dried over sodium sulfate. The organic layer was concentrated under vacuum and the crude product was purified by flash chromatography on silica gel using hexane/ethyl acetate to give of (E)-ethyl 3-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)acrylate as a yellow liquid (0.78 g, 76%). 1HNMR: 400 MHz, DMSO-d6: δ 1.25-1.26 (m, 3H), 1.58-1.62 (m, 2H), 1.76-1.77 (m, 1H), 1.97-2.07 (m, 2H), 2.39-2.42 (m, 1H), 3.73-3.79 (m, 1H), 3.88-3.91 (m, 1H), 4.21 (q, J=7.20 Hz, 2H), 5.87-5.88 (m, 1H), 6.64 (d, J=15.60 Hz, 1H), 7.76-7.77 (m, 2H), 7.81-7.87 (m, 1H), 8.12 (s, 1H), 8.18 (s, 1H). LCMS: RT 1.01 min; LCMS (ES-API), m/z 217 (M-THP).

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