Triphenylphosphine → HCID 86755716, compound

Participants

Reaction Steps

To a solution of 3-(6-bromo-benzo[b]naphtho[2,3-d]thiophen-11-yl)-2,6 difluoro-phenol (0.700, 1.59 mmol), (S)-2-hydroxy-3-phenylpropionic acid, methyl ester (0.572g, 3.17mmol) and triphenylphosphine (0.831g, 3.17 mmol) in dry benzene (10 mL) was added diethylazodicarboxylate (0.50 mL, 3.17 mmol) dropwise at room temperature under a dry nitrogen atmosphere. The reaction mixture was sealed in a pressure bottle and immersed in a pre-heated oil bath at 105° C. and heated for 2.5 hours. After stirring at ambient temperature for 14 hours the reaction mixture was diluted with methylene chloride and combined with silica gel. The solvents were removed and the adsorbate was flash chromatographed (90/10 petroleum ether/ethyl acetate) to give (R)-2-[3-(6-bromo-benzo[b]naphtho[2,3-d]thiophen-11-yl)-2,6-difluoro-phenoxy ]-3-phenyl-propionic acid, methyl ester as an off white solid (0.73g., 76%). To a solution of this methyl ester (0.66g, 1.09 mmol) in tetrahydrofuran (2 mL) and methanol (7 mL) was added a 1 N aqueous solution of potassium hydroxide (1.64mL, 1.64mmol). After stirring for two hours the solvents were removed and the residue was combined with water (50 mL) and acidified with 10% HCl. The solid was extracted into ether and the layers were shaken well together for several minutes before they were separated. The organic layer was washed with water and concentrated to give the title compound as a white solid (0.613 g, 95%): [a]D25 =-13.81 (9.413 mg/mL chloroform); NMR (400 MHz, DMSO-d6): δ13.21 (s, 1H), 8.30 (d, J=8 Hz, 1 H), 8.08 (d, J=8 Hz, 1 H), 7.82 - 7.78 (m, 1 H), 7.62 - 7.41 (m, 4 H), 7.35 - 7.14 (m, 7 H), 6.74 (dd, J=8, 9 Hz, 1 H), 5.17 - 5.11 (m, 1 H), 3.32 - 3.24 (m, 1 H), 3.19 -3.12(m, 1H), NMR indicates that 0.22 mole eq. of benzene is present; MS (+FAB): (M:+): one bromine pattern observed, 588/590 (78%, 75%); Anal. Calc. for C31H19BrF2O3S.0.22 C6 H6: C, 63.99, H, 3.38, N, 0.00. Found: C, 64.52, H, 3.48. N, 0.06.

Provenance & Evidence