Ethyl Acetate → HCID 67401665, compound

Participants

Reaction Conditions

Reaction Steps

Compound 11 (7.70 g, 16.70 mmol, 1 eq), Pd(OAc)2 (378 mg, 1.68 mmol, 0.1 eq) and 1,1′-Bis(diphenylphosphino)ferrocene (dppf) (1.86 g, 3.34 mmol, 0.2 eq) were dissolved in dry DMF (40 mL). K2CO3 (11.54 g, 83.5 mmol, 5 eq) was then added to the reaction mixture and CO gas was bubbled through for 15 min. The reaction mixture was then heated at 60° C. for 8 h under a CO balloon. The reaction mixture was then cooled and partitioned between ethyl acetate and saturated NHCO3. The aqueous layer was acidified with a 10% aqueous solution of citric acid and extracted with ethyl acetate (4×75 mL). The organic layer was washed with brine, dried over Na2SO4 and the solvent was evaporated to give the crude carboxylic acid as a tan-coloured solid (4.89 g). The acid was dried over P2O5 and was used in the next step without purification. The crude acid was dissolved in dry THF (70 mL) and cooled in an ice bath. The reaction was charged with BH3-DMS complex (10 M, 6.96 mL, 68.47 mmol, 4 eq) added dropwise. The reaction mixture was warmed to room temperature over 2 h. A solution of saturated NaHCO3 was added dropwise until the bubbling ceased. Ethyl acetate (70 mL) was added and the organic layer was separated and dried over Na2SO4 and then reduced. The crude product was purified on a silica column (3:2 hexane:ethyl acetate followed by 2:3 hexanes:ethyl acetate) to give 12 (3.56 g, 62%) as a white solid. [α]D25+50.56° (C=0.99, CHCl3). 1H NMR (400 MHz, CDCl3) δ 7.41-7.29 (m, 5H), 7.29-7.23 (m, 2H), 7.08 (d, J=8.0 Hz, 2H), 5.14-4.87 (m, 2H), 4.65 (dd, J=10.2, 5.8 Hz, 3H), 3.70 (d, J=18.6 Hz, 3H), 3.10 (qd, J=13.9, 5.8 Hz, 2H), 1.86 (t, J=5.8 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 172.17 (s), 155.86 (s), 140.04 (s), 136.45 (s), 135.29 (s), 129.68 (s), 128.75 (s), 128.43 (s), 128.32 (s), 127.49 (s), 67.22 (s), 65.20 (s), 55.03 (s), 52.59 (s), 38.12 (s). ESIMS calculated for C19H21NO5Na [M+Na]+366.13, found: 366.13; mp 74-77° C.

Provenance & Evidence