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0 °C

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.

1. concentrationThe mixture was concentrated to dryness
2. additionmixed with brine (25 mL) and glacial acetic acid (0.65 mL)
3. extractionextracted with CHCl3 (2×100 mL)
4. dry with materialThe extracts were dried over MgSO4
5. additiontreated with Et3N (1 g)
6. concentrationconcentrated to dryness
7. additiontreated sequentially with potassium carbonate (11 g), THF (20 mL), water (20 mL), and di-tert-butyl dicarbonate (8 g)
8. stirringThe mixture was stirred overnight
9. additiondiluted with more THF (50 mL)
10. additiontreated with NaCl (20 g)
11. customThe organic layer was separated
12. dry with materialdried over MgSO4
13. concentrationconcentrated to an oil which
14. customwas purified by silica chromatography