Trifluoroacetic acid → HCID 15157643, compound

Participants

Reaction Conditions

Reaction Steps

Compound 506a (900 mg, 3.58 mmol) was dissolved in THF (15 mL) under an atmosphere of Argon. The solution was cooled to −40° C. over 10 min and secbutyllithium (1.4 M, 5.37 mL) was added slowly as to maintain an internal temperature of <−25° C. After reaching 1 equiv of sec-butyllithium (2.7 mL) the reaction mixture turned a bright yellow signifying deprotonation of the amide nitrogen. The reaction mixture was then cooled to −50° C. and a solution of N-methoxy-N-methylacetylamide 407 (442.8 mg, 4.78 mmol) in THF (3 mL) was added over 5 min. The reaction mixture was warmed to −10° C. over 30 min. The mixture was partitioned between Et2O (75 mL) and 0.5 N HCl (75 mL). The aqueous layer was separated and extracted an additional two times with Et2O (50 mL). The Et2O phases were combined and washed with brine (75 mL) and then dried over Na2SO4 to yield a dark-brown oil. The crude intermediate was dissolved in DCM (20 mL). TFA (3 mL) was added to the mixture which was then stirred at rt for 48 h. Upon completion, the reaction mixture was added to a separatory funnel and washed with NaHCO3 (50 mL) followed by brine (50 mL). The organic layer was separated and then dried over Na2SO4 to provide a crude black oil (1 g) which was purified by chromatography (0% to 20% EtOAc/hexanes) to yield a brown solid (335 mg, 53%): mp 88-90° C. TLC Rf 0.48 (20% EtOAc/hexanes). 1H NMR (600 MHz, CDCl3) δ 7.72 (s, 1H), 7.16-7.14 (d, 1H, J=8.64 Hz), 6.99 (d, 1H, J=2.4 Hz), 6.77-6.75 (dd, 1H, J1=8.7 Hz, J2=2.4 Hz), 6.13 (s, 1H), 4.07-4.04 (q, 2H, J=6.96 Hz), 2.41 (s, 3H), 1.43-1.40 (t, 3H, J=6.96 Hz). 13C NMR (150 MHz, CDCl3) δ 153.3, 135.8, 131.2, 129.5, 111.33, 110.75, 103.1, 100.3, 64.2, 15.1, 13.8. Elemental analysis calculated for C11H13NO: C, 75.40; H, 7.48; N, 7.99. Found: C, 75.11; H, 7.64; N, 7.46.

Provenance & Evidence