2-Azidoethanol → 1-methylethyl {(2S,4R)-1-acetyl-6-[1-(2-hydroxyethyl)-1H-1,2,3-triazol-4-yl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl}carbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-methylethyl[(2S,4R)-1-acetyl-6-ethynyl-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation, see Intermediate 58) (100 mg, 0.318 mmol) in a mixture of N,N-dimethylformamide (DMF) (1.8 mL) and methanol (0.200 mL) were successively added 2-azidoethanol (55.4 mg, 0.636 mmol) and copper(I) iodide (3.03 mg, 0.016 mmol). The resulting mixture was stirred at 100° C. under microwave irradiation for 2 h then cooled to room temperature. The reaction mixture was partitioned between EtOAc and brine and the layers were separated. The aqueous phase was extracted with EtOAc (3×) and the combined organic layers were washed with brine, dried over a Na2SO4 cartridge and concentrated in vacuo. Purification of the residue on SP4 using a 10 G silica cartridge (gradient: 2 to 10% MeOH in DCM) gave 1-methylethyl {(2S,4R)-1-acetyl-6-[1-(2-hydroxyethyl)-1H-1,2,3-triazol-4-yl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl}carbamate (83 mg, 0.198 mmol, 62%) as an off white solid.

Provenance & Evidence