Trifluoroacetic acid → (3S)-4-{[(9H-Fluoren-9-yl)methoxy]carbonyl}morpholine-3-carboxylic acid

Participants

Reaction Steps

Trifluoroacetic acid (10 mL) was added to a solution of (S)-4-(tert-butoxycarbonyl) morpholine-3-carboxylic acid (5.00 g, 21.64 mmol) in CH2Cl2 (40 mL) dropwise at 0° C. and the reaction mixture was stirred at room temperature for 5 h. The reaction mixture was concentrated to dryness and the crude residue (2.80 g, 21.30 mmol) was dissolved in a mixture of dioxane (30 mL) and water (10 mL). The suspension was cooled to 0° C., FMOC-Cl (6.60 g, 25.60 mmol) and K2CO3 (11.60 g, 84.2 mmol) were added, and the mixture was stirred at room temperature for 3 h. The reaction mixture was concentrated, diluted with water (20 mL) and acidified with 1M aqueous HCl (30 mL) to pH 2-3. The resulting mixture was extracted with EtOAc (3×50 mL). The combined organic layers were washed with brine solution (50 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford the title compound (6.41 g) as colorless oil which was used in the next step without further purification.

Provenance & Evidence