Compound 3a

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Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

Tetra-n-butylammonium fluoride (TBAF, 1.0 M in THF, 12.0 mL, 12.0 mmol) was added to a solution of TBS-ether S1 (Francisco, C. G.; Martín, C. G.; Suárez, E. J. Org. Chem. 63, 2099 (1998)) (2.39 g, 5.85 mmol) and AcOH (1.30 mL, 22.7 mmol) in THF (20.0 mL) at room temperature. The reaction mixture was stirred for 12 h at room temperature, and then saturated aqueous NH₄Cl (50 mL) was added. The resultant mixture was extracted with EtOAc (70 mL x2). The combined organic layers were washed with brine (30 mL), dried over Na₂SO₄, filtered and concentrated. The residue was filtered through a pad of silica gel (40 g, EtOAc). The filtrate was concentrated to afford the crude alcohol S2 (2.26 g), which was used in the next reaction without further purification. (2,2,6,6-Tetramethyl-piperidin-1-yl)oxyl (TEMPO, 183 mg, 1.17 mmol) and PhI(OAc)₂ (5.65 g, 17.6 mmol) were added to a solution of the above crude alcohol S2 (2.26 g) in MeCN (6.0 mL) and H₂O (6.0 mL) at room temperature. The reaction mixture was stirred for 2 h at room temperature, and then saturated aqueous Na₂S₂O₃ (20 mL) was added. After being stirred for 20 min at room temperature, the resultant mixture was extracted with CHCl₃ (30 mL x5). The combined organic layers were dried over Na₂SO₄, filtered and concentrated. The residue was purified by flash column chromatography on silica gel (50 g, hexane/EtOAc/AcOH 3/1/0 to 0/100/1) to afford carboxylic acid 3a (1.69 g, 5.48 mmol) in 94% yield over 2 steps: pale yellow solid; mp 114-116 °C; [α]_D²⁴ = –55.5 (c 1.00, CHCl₃); IR (film) 2991, 2942, 1731, 1288, 1260, 1211, 1095, 1054, 957 cm^-1; ¹H NMR (400 MHz, CDCl₃) δ 1.37 (3H, s, CH₃ of acetonide), 1.53 (3H, s, CH₃ of acetonide), 4.76 (1H, s, H4), 4.85 (1H, d, J = 5.9 Hz), 5.29 (1H, d, J = 5.9 Hz), 6.50 (1H, s, H1), 7.39 (2H, m, aromatic), 7.55 (1H, m, aromatic), 7.88 (2H, m, aromatic), 8.44 (1H, br s, CO₂H); ¹³C NMR (100 MHz, CDCl₃) δ 24.9, 26.3, 81.8, 84.1, 84.7, 102.2, 113.7, 128.5 (2C), 128.9, 129.7 (2C), 133.6, 164.6, 173.4; HRMS (ESI) calcd for C₁₅H₁₆O₇Na [M+Na]⁺ 331.0788, found 331.0790.