Hexane → HCID 68173881, compound

Participants

Reaction Conditions

Reaction Steps

A solution of n-butyllithium in hexane (2.50 M; 176.52 mL, 441.29 mmol) was added dropwise over 20 mins to a solution of 2-bromofluorobenzene (49.00 mL, 451.88 mmol) in THF (670 mL) under a N2 atmosphere at −78° C. The temperature of the reaction was kept below −60° C. during the addition. The yellow solution was stirred at −78° C. for 30 mins. (S)-2-((1-fluorobut-3-en-2-yl)oxy)-N-methoxy-N-methylacetamide (67.50 g, 353.03 mmol) was added dropwise as a solution in THF (100 mL) keeping the internal temperature below −60° C. The reaction was stirred at −78° C. for 45 mins. Aqueous NH4Cl (200 mL) was added to the reaction solution and was allowed to warm up to RT and EtOAc (700 mL) was added. The two layers were separated. The aqueous layer was extracted with EtOAc (300 mL). The combined organic portions were washed with water 9300 mL), dried over MgSO4, (40 g) and concentrated. The crude product was purified by silica gel column chromatography (1% to 10% EtOAc in hexanes) to obtain the title compound as a yellow liquid (63.78 g, 80%). 1H-NMR (400 MHz, CDCl3) δ ppm 4.16-4.31 (m, 1H) 4.42-4.51 (m, 1H) 4.54-4.61 (m, 1H) 4.67-4.88 (m, 2H) 5.35-5.52 (m, 2H) 5.80 (ddd, J=17.43, 10.29, 7.26 Hz, 1H) 7.11-7.19 (m, 1H) 7.24-7.31 (m, 1H) 7.49-7.60 (m, 1H) 7.92-8.00 (m, 1H).

Provenance & Evidence