Ethyl 2-bromobenzoate → Ethyl 2-(3-(3-(((2-tetrahydropyranyl)oxy)methyl)phenyl)-3-oxopropyl)benzoate

Participants

Reaction Conditions

Reaction Steps

The allylic alcohol of Step 10 (24.8 g, 100 mmol) and ethyl 2-bromobenzoate (25.2 g, 110 mmol) were dissolved in DMF (200 mL). LiCl (4.2 g, 100 mmol), LiOAc.2H2O (25.5 g, 250 mmol) and n-Bu4N+Cl- (55 g, 200 mmol) were added and the resulting mixture was degassed three times. Pd(OAc)2 (1 g) was then added and the mixture was degassed three more times before heating it at 100° C. with stirring for 1 hour. After cooling to r.t., the reaction mixture was poured onto H2O (600 mL), 10% aq. NaHCO3 (200 mL) and Et2O. The crude product was extracted with Et2O (2×), washed with H2O and brine, and dried over Na2SO4 before concentrating in vacuo. Purification on a short silica gel column (20% EtOAc in hexanes) gave 34 g (86%) of the title compound. 1H NMR (CD3COCD3): δ8.02 (1H, br s), 7.92 (1H, d), 7.88 (1H, d), 7.65 (1H, d), 7.50 (3H, m), 7.32 (1H, br t), 4.8 (1H, d), 4.70 (1H, br s), 4.54 (1H, d), 4.3 (2H, q), 3.82 (1H, m), 3.50 (1H, m), 3.35 (2H, m), 1.9-1.45 (8H, m), 1.32 (3H, t).

Provenance & Evidence