Dimethyl Sulfoxide → Biphenyl-2-ylcarbamic Acid 1-[2-(4-Formylphenylcarbamoyl)ethyl]piperidin-4-yl Ester

A mixture of biphenyl-2-ylcarbamic acid 1-[2-(4-aminomethylphenylcarbamoyl) ethyl]piperidin-4-yl ester (1 g, 2.7 mmol; prepared as described in Preparation 14), 4-aminobenzyl alcohol (498 mg, 4.05 mmol), HATU (1.54 g, 4.05 mmol) and DIPEA (1.41 mL, 8.1 mmol) in DCM (14 mL) was stirred at room temperature for 2 hours. The reaction mixture was diluted with 100 mL of DCM and washed first with a 1:3 mixture of 1N HCl/water (100 mL), then brine (100 mL). The organic layer was dried over MgSO4, filtered and concentrated. The residue was dissolved in DCM (100 mL) and the solution was cooled to −5° C. DIPEA (1.1 mL, 6.33 mmol) and DMSO (1.5 mL, 21.1 mmol) were added to the solution, followed by sulfur trioxide pyridine complex (1 g, 6.33 mmol). The reaction mixture was stirred at 0° C. for 1 hour then washed with a saturated solution of sodium bicarbonate (100 mL) and brine (100 mL). The organic layer was dried over MgSO4, filtered and concentrated to give 0.84 g of the title intermediate (66% yield) as an oil.

1. washwashed first with a 1:3 mixture of 1N HCl/water (100 mL)
2. dry with materialThe organic layer was dried over MgSO4
3. filtrationfiltered
4. concentrationconcentrated
5. dissolutionThe residue was dissolved in DCM (100 mL)
6. temperaturethe solution was cooled to −5° C
7. stirringThe reaction mixture was stirred at 0° C. for 1 hour
8. washthen washed with a saturated solution of sodium bicarbonate (100 mL) and brine (100 mL)
9. dry with materialThe organic layer was dried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated

ORD record

ord-35721a062e184c70af55503317ad459f

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07728144B2