Sodium Hydroxide → 2-[2-(1-tert-Butoxycarbonylpiperidin-4-yloxy)-4-(dimethylamino)phenyl]-4H-thieno[3,4-d][1,3]oxazin-4-one

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Reaction Conditions

Reaction Steps

A solution of methyl 4-[2-(1-tert-butoxycarbonyl-piperidin-4-yloxy)-4-(dimethylamino)benzoylamino]thiophene-3-carboxylate (2.3 g, 4.6 mmol) in MeOH (100 mL) and THF (50 mL) was treated with a solution of 1 N aqueous NaOH (10 mL) at 60° C. for 24 h. The mixture was concentrated to dryness, mixed with brine (25 mL) and glacial acetic acid (0.65 mL), then extracted with CHCl3 (2×100 mL). The extracts were dried over MgSO4, cooled to 0° C. and treated with Et3N (1 g) followed by a 2 M CH2Cl2 solution of oxalyl chloride (3.5 mL). The mixture was stirred overnight, concentrated to dryness, and treated sequentially with potassium carbonate (11 g), THF (20 mL), water (20 mL), and di-tert-butyl dicarbonate (8 g). The mixture was stirred overnight, diluted with more THF (50 mL) and treated with NaCl (20 g). The organic layer was separated, dried over MgSO4, and concentrated to an oil which was purified by silica chromatography using 15% EtOAc in hexanes to give 2 g of product as an oil.

Provenance & Evidence