Citric Acid → HCID 68162260, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 1,1-dimethylethyl 3-[4-(4-{[1-methyl-3-({[(1-methylethyl)oxy]carbonyl}amino)-3-oxopropyl]amino}phenyl)-1H-imidazol-1-yl]propanoate (for a preparation see Intermediate 95) (1.53 g, 3.34 mmol) in ethanol (20 mL) was cooled to −15° C. then treated with sodium borohydride (114 mg, 3.0 mmol) followed by magnesium chloride (1M in water, 3.67 mL, 3.67 mmol) maintaining the temperature below −10° C. The mixture obtained was stirred at a temperature lower than 0° C. for 1 h then at room temperature for 1 h. The suspension formed was poured onto a stirred mixture of citric acid (1.6 g, 8.34 mmol), HCl (1M in water, 25 mL) and DCM (15 mL) and the mixture obtained was stirred at room temperature for 30 min. The layers were separated and the aqueous phase was basified by the addition of solid K2CO3 then was extracted with AcOEt (3×20 mL). The combined organic phases (DCM+EtOAc) were washed with water then brine dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 0 to 2% MeOH in DCM) gave 1,1-dimethylethyl 3-{(cis)-4-[2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]-1H-imidazol-1-yl}propanoate (1.46 g, 3.30 mmol, 99%) as an orange oil.

Provenance & Evidence