Triethylamine → (2S)-2-[(1S)-5-methoxy-2,3-dihydro-1H-inden-1-yl]butanoic Acid

Participants

Reaction Steps

A solution of the product obtained in Example 3 (105 g, 453 mmol), ClRh(PPh3)3 (21.0 g, 5% eq.) and triethylamine (68.8 g, 679.5 mmol) in EtOH (945 mL) and THF (105 mL) was shaken in a 2-L pressure bottle under 60 psi H2 for 16 hours. The solvents were removed at a reduced pressure. The resulting mixture was stirred in 1.5 L of 1N HCl solution and 1.5 L CH2Cl2. The aqueous layer was extracted with CH2Cl2 (2×250 mL). The combined CH2Cl2 layers were washed with 1 L of 1N HCl solution and stirred with 1 L of 1N NaOH solution. The organic layer was extracted with 1N NaOH solution (2×0.5 L). The combined aqueous layer was washed with CH2Cl2 (2×250 mL), and acidified (pH 2.0–3.0) by a slow addition of conc. HCl solution at below 15° C. The acidic mixture was extracted with CH2Cl2 (2×1.5 L), and washed with water (2×0.5 L) until pH 5.0–6.0. After washing with brine and drying over anhydrous Na2SO4, solvent was evaporated under a reduced pressure. The product (101.0 g, 95% yield, 96.8% ee) was obtained as a light yellow oil. 1H NMR (DMSO-d6) δ12.20(s, 1H), 7.04(d, 1H), 6.78(d, 1H), 6.66(dd, 1H), 3.70(s, 3H), 3.28(m, 1H), 2.72(m, 2H), 2.32(m, 1H), 2.06(m, 1H), 1.80(m, 1H), 1.50(m, 1H), 1.36(m, 1H), 0.82(t, 3H).

Provenance & Evidence