Hydrochloric Acid → 2-((2-Chlorophenyl)(methyl)carbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxylic acid

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Reaction Conditions

Reaction Steps

To a solution of methyl 2-((2-chlorophenyl)(methyl)carbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxylate 138 (45 mg, 0.11 mmol) in 1.0 mL THF and 1.0 mL water in a 20 mL scintillation vial was added LiOH (monohydrate, 200 mg). The vessel was sealed and heated at 50° C. over night. The reaction mixture was cooled to room temperature, acidified to pH 2 with 2N HCl, and extracted with ethylacetate. The combined organic extracts were dried over Na2SO4 and concentrated to give the crude 2-((2-chlorophenyl)(methyl)carbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxylic acid. To a solution of this acid in 2 mL DMF was added DIPEA (0.15 mL) and HATU, (N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate, 75 mg) followed by ammonium chloride (34 mg). The whole was stirred at room temperature for 2 hours, diluted with water and extracted with ethylacetate. The combined organics were concentrated and the residue purified by reverse phase HPLC to give 137 as a colorless solid. 1H NMR (500 MHz, DMSO-d6) δ 7.94 (br s, 1H), 7.66 (m, 2H), 7.54-7.46 (m, 4H), 7.35 (m, 1H), 6.59 (m, 1H), 4.21 (m, 2H), 3.26 (m, 3H, obstructed by water), 2.98 (m, 2H). MS: (ESI+) 413.1

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