4-(ethoxycarbonylmethyl)phenylboronic acid, pinaco

Ethyl (4-bromophenyl)-acetate (100 g, 411 mmol) Z?-(pinacolato)diboron (125.4 g, 493.7 mmol) and potassium acetate (125.4 g, 493.7 mmol) were charged to a 2 L round bottom flask. 1, 4-Dioxane (1 L) was added and the mixture was stirred under a nitrogen EPO Intermediate 1A ethyl 2-(4-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl)phenyl)acetate [0452] [0453] To a vial containing a degassed (3× vacuum/Ar) mixture of ethyl 2-(4-bromophenyl)acetate (1 g, 4.11 mmol), bis(pinacolato)diboron (1.25 g, 4.94 mmol), and potassium acetate (1.21 g, 12.3 mmol) in dioxane (10 mL), was added PdClIn a 350 mL reaction vial, ethyl 2-(4-bromophenyl)acetate (25 g, 103 mmol), BISPIN (31.3 g, 123 mmol) and potassium acetate (20.2 g, 206 mmol) were combined with 1, 4 dioxane (190 mL) to give a white suspension. The mixture was purged with nitrogen for 5 min, PdClA solution of ethyl 2-(3-bromophenyl)acetate (1 g, 4.1 mmol) in dioxane (20 mL) was degassed with argon, to this solution (bis-pinacolato)diboron (1.25 g, 4.9 mmol), KOAc (1.21 g, 12 mmol) and Pd(dppf)Step 1: Ethyl 2-(4-(4, 4, 5, 5-tetramethyl- 1 , 3, 2-dioxaborolan-2-yl)phenyl)acetate A suspension of ethyl 2-(4-bromophenyl)acetate (500 mg, 2.06 mmol), bis(pinacolato)diboron (1.05 mg, 4.11 mmol), and potassium acetate (606 mg, 6.17 mmol) in dioxane (4 mL) was degassed with bubbling nitrogen. PdC12(dppf)-CH2C12adduct (84.0 mg, 0.100 mmol) was added, and the reaction was heated to 85 °C for 4 h. The reaction was diluted with ethyl acetate (30 mL) and filtered through Celite. The organic layer was washed with brine, separated, and dried with sodium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (40 g column, gradient from 0percent to 20percent EtOAc/hexanes) to give the title compound (471 mg, 79percent) as a colorless oil. ‘H NMR (400MHz, CDC13) ö 7.79 (d, J7.9 Hz, 2H), 7.32 (d, J=7.9 Hz, 2H), 4.16 (q, J=7.1 Hz, 2H), 3.64 (s, 2H), 1.36 (s, 12H), 1.26 (t, J=7.2Hz, 3H); LCMS (M+H) = 291.3; HPLC RT = 1.03 mill (Column: BEH C18 2.1 x 50 mm;Mobile Phase A: Water with 0.05percent TFA; Mobile Phase B: Acetonitrile with 0.05percent TFA;Gradient: 2-98percent B over 1.6 mm; Flow: 0.8 mL/min).A suspension of ethyl 2-(4-bromophenyl)acetate (500 mg, 2.06 mmol), bis(pinacolato)diboron (1.05 mg, 4.11 mmol), and potassium acetate (606 mg, 6.17 mmol) in dioxane (4 mL) was degassed with bubbling nitrogen. PdClPREPARATION 132-(4-(4, 4, 5, 5-tetramethyl-l, 3, 2-dioxaborolan-2-yl)phenyl)acetic acid (0.18 mgs, 0.67 mmol) was dissolved in dry THF (7 mis). To this solution was added ethanol (0.037 mis, 0.81 mmol) and resin bound triphenylphosphine (0.93 g, 2.014 mmol, 2.16 mmol/g). This mixture was gentyl stirred at room temperature for 20 minutes. Diisopropylazidodicarboxylate (0.34 mis, 1.68 mmol) was then added and the mixture was stirred at room temperature for one hour, then filtered, and the resin rinsed several times with EtOAc. The filtrate was concentrated and the resulting material was purified by Flash 40 Biotage (4OM cartridge, 30percent EtOAc/Hexanes) to give 137 mgs (70percent) of ethyl 2-(4-(4, 4, 5, 5-tetramethyl-l, 3, 2-dioxaborolan-2-yl)phenyl)acetate as an orange oil.To a 500 ml round bottom flask was added 5-bromo-N-(1-methylimidazol-4-yl)pyrimidin-2-amine (12, 2.00 g, 7.87 mmol) followed by THF (100 ml). The solid was allowed to dissolve and to the resulting solution was added (1.53 g), the compound obtained in (2.00 g), chloro(2-dicyclohexylphosphino-2', 4', 6'-isopropyl-1, 1'-biphenyl) [2-(2'-amino-1, 1'-biphenyl)]palladium(II) (0.376 g) and potassium phosphate (3.04 g) was suspended in toluene (38 mL) and water (2mL), and stirred for 3 hours and 30 minutes at 100 C. Ethyl acetate was added to the reaction mixture, and the mixture was washed with water and saturated brine. The organic layer wasdried over sodium sulfate, and concentrated under reduced pressure, the residue was purified by silica gel column chromatography (ethyl acetate / hexane) to give the title compound (2.27 g) as a pale yellow amorphous solid.

Molecular Weight:290.2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:5
Exact Mass:290.1689394
Monoisotopic Mass:290.1689394
Topological Polar Surface Area:44.8
Heavy Atom Count:21
Complexity:357
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes