Triethylamine → HCID 71270605, compound

Participants

Reaction Steps

To a solution of (1S,3S,4S)-3-(benzyloxy)-4-(benzyloxymethyl)cyclopentanol (23) (340.00 g, 1088.3 mmol) in methylene chloride (3400 mL) and triethylamine (455.08 mL, 3265.0 mmol) at 0° C., was added methanesulfonyl chloride (92.661 mL, 1197.2 mmol) slowly under a blanket of nitrogen, maintaining a temperature of less than 10° C. The reaction was allowed to warm to ambient temperature and stirred for 1 hour. HPLC indicated complete consumption of starting material. The reaction mixture was cooled to 0° C. and quenched with water (1700 mL) maintaining a temperature of less than 10° C. The organics were separated and extracted twice with water (1700 mL) and twice with saturated sodium bicarbonate in water (1700 mL). Sodium sulfate (50 g) was added and the mixture stirred for 10 minutes. The slurry was filtered and the filtrate concentrated to give a brown oil. The oil was taken up in tetrahydrofuran (3400 m) to which tetrabutylammonium acetate (656.28 g, 2176.7 mmol) was added and the mixture was stirred at ambient temperature for 20 hours. HPLC analysis indicated complete consumption of starting material. The reaction mixture was concentrated to ˜2 volumes (700 mL), and ethyl acetate (3400 mL) was added and mixture was extracted three times with water (1700 mL) and once with saturated sodium chloride in water (1700 mL). The organics were concentrated and the resulting residue was eluted through a plug of silica gel (1 kg) with 0-20% ethyl acetate/hexane [ethyl acetate (4 L)+hexane (16 L)]. The desired fractions were combined and concentrated to give a brown residue. To the resulting residue, methanol (4000 mL) was added followed by a mixture of sodium hydroxide (130.59 g, 3265.0 mmol) in water (2000 mL), and the reaction mixture was stirred at ambient temperature for 1 hour. HPLC analysis indicated complete consumption of starting material. The majority of the methanol in the reaction mixture was concentrated and water (1700 mL) was added. The mixture was extracted three times with ethyl acetate (3×1700 mL). The combined organics were washed with saturated sodium chloride in water (1700 mL) and dried over sodium sulfate (50 g). The resulting slurry was filtered and concentrated to give a light brown oil (238 g, 70%). 1H NMR (300 MHz, CD3OD, δ): 7.28 (m, 10H), 4.50 (m, 3H), 4.38 (m, 2H), 4.12 (t, 1H), 3.70 (m, 1H), 3.45 (m, 1H), 2.52 (m, 1H), 2.11 (m, 1H) and 1.75 (m, 3H).

Provenance & Evidence