Phenylmethyl 3,6-dihydro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1(2H)-pyridinecarboxylate

The title compound was prepared according to the procedure described in Tetrahedron Lett. 2000, 41 3705. Bis(pinacolato)diborane (338 mg, 1.33 mmol), potassium acetate (356 mg, 3.63 mmol), [1, 1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (PdCl2dppf; 30 mg, 0.04 mmol), and 1, 1'-bis(diphenylphosphino)ferrocene (20 mg, 0.04 mmol) were combined and treated with the product from Example 58A (440 mg, 1.21 mmol) in degassed 1, 4-dioxane (7 mL). The reaction mixture was heated at 80° C. for 16 hours, allowed to cool to 23° C., diluted with water, and extracted with dichloromethane (3.x.). The dichloromethane extracts were combined, dried over sodium sulfate, filtered, and the filtrate concentrated under reduced pressure. The residue was chromatographed on flash silica gel (20percent ethyl acetate:hexanes) to provide the title compound (323 mg, 78percent yield). 1H NMR (300 MHz, CDCl3) δ1.25 (s, 12H), 2.24 (m, 2H), 3.52 (dd, 2H, J=5.7, 5.7 Hz), 4.03 (dd, 2H, J=6 Hz), 5.14 (s, 2H), 6.46 (br m, 1H), 7.32 (m, 5H); MS (ESI) m/e 344 (M+H)+.The title compound was prepared according to the procedure described in Tetrahedron Lett. 2000, 41 3705. Bis(pinacolato)diborane (338 mg, 1.33 mmol), potassium acetate (356 mg, 3.63 mmol), [1, 1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (PdCl2dppf; 30 mg, 0.04 mmol), and 1, 1'-bis(diphenylphosphino)ferrocene (20 mg, 0.04 mmol) were combined and treated with the product from Example 58A (440 mg, 1.21 mmol) in degassed 1, 4-dioxane (7 mL). The reaction mixture was heated at 80 C. for 16 hours, allowed to cool to 23 C., diluted with water, and extracted with dichloromethane (3). The dichloromethane extracts were combined, dried over sodium sulfate, filtered, and the filtrate concentrated under reduced pressure. The residue was chromatographed on flash silica gel (20percent ethyl acetate:hexanes) to provide the title compound (323 mg, 78percent yield). 1H NMR (300 MHz, CDCl3) ' 1.25 (s, 12H), 2.24 (m, 2H), 3.52 (dd, 2H, J=5.7, 5.7 Hz), 4.03 (dd, 2H, J=3, 6 Hz), 5.14 (s, 2H), 6.46 (br m, 1H), 7.32 (m, 5H); MS (ESI) m/e 344 (M+H)+.Step 2 benzyl 4-(4, 4, 5, 5-tetramethyl-1 , 3, 2-dioxaborolan-2-yl)-5, 6-dihydropyridine-1 (2H)- carboxylate (173); [0356] A mixture of bis(pinacolato)diboron (3 14 g, 12 38 mmol), 172 (5 26 g, 12 38 mmol), DPPF (0 206 g, 0 371 mmol), PdCITetrahydropyridine 2 was prepared in 3 steps starting with the deprotection of 1 using Method 3. The resulting HCl amine salt was dissolved in dichloromethane (0.2 M). Benzyl chloroformate (1.2 equiv) was added followed by triethylamine (3.0 equiv). The reaction was allowed to stir at room temperature for 2h after which point it was diluted with IN HCl and extracted with excess dichloromethane. The organic layer was dried over MgSψ4 and concentrated to provide the desired carbamate in quantitative yield, which was converted directly to boronic acid 2 using Method 2. [M-H]- = 260.1 m/z. Activity: B2nd step: under the protection of nitrogen, the 1M isopropyl magnesium chloride-lithium chloride (88 ml, 88mmol) into the reaction bottle, temperature control -15 ° C to -10 °C, dropwise N-Cbz-1, 2, 5, 6-tetrahydro-pyridine-4-bromo, 2-methyl tetrahydrofuran (90 ml) solution, stirring finishing joining 1-2 hours. After the end of the exchange, then drop by adding methoxy boronic acid pinacone ester (14.2g, 90mmol), subsequently maintain the reaction at room temperature overnight. Adding 10percent hydrochloric acid aqueous solution quenching reaction, adjusting PH= 4-5, adding 220 ml ethyl acetate, saturated salt water an organic layer, the organic layer after evaporation to dryness, add ethanol/heptane 10:1 obtained after pulping 19.2g a buff solid N-Cbz-1, 2, 5, 6-tetrahydro-pyridine-4-boronic acid frequency that alcohol ester, GC: 99.6percent, yield: 56percent.[1245] The title compound was prepared according to the procedure described in Tetrahedron Lett. 2000, 41 3705. Bis(pinacolato)diborane (338 mg, 1.33 mmol), potassium acetate (356 mg, 3.63 mmol), [1, 1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (PdCl2dppf; 30 mg, 0.04 mmol), and 1, 1'-bis(diphenylphosphino)ferrocene (20 mg, 0.04 mmol) were combined and treated with the product from Example 58A (440 mg, 1.21 mmol) in degassed 1, 4-dioxane (7 mL). The reaction mixture was heated at 80 C. for 16 hours, allowed to cool to 23 C., diluted with water, and extracted with dichloromethane (3×). The dichloromethane extracts were combined, dried over sodium sulfate, filtered, and the filtrate concentrated under reduced pressure. The residue was chromatographed on flash silica gel (20% ethyl acetate:hexanes) to provide the title compound (323 mg, 78% yield). 1H NMR (300 MHz, CDCl3) delta1.25 (s, 12H), 2.24 (m, 2H), 3.52 (dd, 2H, J=5.7, 5.7 Hz), 4.03 (dd, 2H, J=6 Hz), 5.14 (s, 2H), 6.46 (br m, 1H), 7.32 (m, 5H); MS (ESI) m/e 344 (M+H)+.The title compound was prepared according to the procedure described in Tetrahedron Lett. 2000, 41 3705. Bis(pinacolato)diborane (338 mg, 1.33 mmol), potassium acetate (356 mg, 3.63 mmol), [1, 1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (PdCl2dppf; 30 mg, 0.04 mmol), and 1, 1'-bis(diphenylphosphino)ferrocene (20 mg, 0.04 mmol) were combined and treated with the product from Example 58A (440 mg, 1.21 mmol) in degassed 1, 4-dioxane (7 mL). The reaction mixture was heated at 80 C. for 16 hours, allowed to cool to 23 C., diluted with water, and extracted with dichloromethane (3). The dichloromethane extracts were combined, dried over sodium sulfate, filtered, and the filtrate concentrated under reduced pressure. The residue was chromatographed on flash silica gel (20% ethyl acetate:hexanes) to provide the title compound (323 mg, 78% yield). 1H NMR (300 MHz, CDCl3) ' 1.25 (s, 12H), 2.24 (m, 2H), 3.52 (dd, 2H, J=5.7, 5.7 Hz), 4.03 (dd, 2H, J=3, 6 Hz), 5.14 (s, 2H), 6.46 (br m, 1H), 7.32 (m, 5H); MS (ESI) m/e 344 (M+H)+.Step 2 benzyl 4-(4, 4, 5, 5-tetramethyl-1 , 3, 2-dioxaborolan-2-yl)-5, 6-dihydropyridine-1 (2H)- carboxylate (173); [0356] A mixture of bis(pinacolato)diboron (3 14 g, 12 38 mmol), 172 (5 26 g, 12 38 mmol), DPPF (0 206 g, 0 371 mmol), PdCI2(dppf)-CH2CI2 adduct (0 303 g, 0 371 mmol) and potassium acetate (2 430 g, 24 76 mmol) was heated at 90 0C in 1 , 4-dioxane (60 mL) for 16 hours It was then diluted with water (200ml) and extracted with ethyl acetate (3x), dried overNa2SO4, filtered and then purified by silica gel chromatography (Flash, 20Og silica and 10 to20% ethyl acetate in hexanes) to give 173 (1 86 g, 5 42 mmol, 43 8 % yield) LRMS (E-Sl)(calc ) 343 2 (found) 344 3 (MH)+

Used in organic synthesis, also used as a solvent

Molecular Weight:343.2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:4
Exact Mass:343.1954885
Monoisotopic Mass:343.1954885
Topological Polar Surface Area:48
Heavy Atom Count:25
Complexity:510
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes