Methanol → HCID 131722700, compound

Participants

Reaction Conditions

Reaction Steps

2-Methyl-3-(R)-((tert-butyldimethylsilyloxy)methyl)-4-(S)-(3-fluorophenyl)-1-tert-butoxycarbonylpyrrolidine (210 mg, 0.5 mmol, from Step B) was dissolved in 6 mL of a solution of 1% HCl in methanol and heated to 50° C. overnight. The solution was concentrated and converted to the free base by solid phase extraction (column: Varian SCX, loading: methanol, elution: 2M ammonia in methanol). This material (60 mg, 0.29 mmol) was dissolved in 1 mL of CH2Cl2. Diisopropylethylamine (0.061 mL, 0.35 mmol) was added, followed by hydroxy ester 9 (102 mg, 0.29 mmol). The reaction mixture was stirred under nitrogen for 1.5 h, and was then diluted with CH2Cl2, washed with 1N NaOH and dried over Na2SO4. The solution was concentrated and purified by preparative HPLC (column: YMC combiprep ODS-A 20×50 mm, gradient: 10% acetonitrile/water w/0.1% TFA to 100% acetonitrile/water w/0.1% TFA over 8 min, then ramp to 10% acetonitrile/water w/0.1% TFA over 2 min, flow: 20 mL/min) to afford 87 mg (73% yield) of the title compound. 1H NMR (400 MHz, CDCl3) δ0.00-0.08 (m, 1H), 0.15-0.21 (m, 1H), 0.36-0.43 (m, 1H), 0.43-0.55 (m, 1H), 0.62-0.75 (m, 1H), 1.55 (d, 3H), 1.74-1.81 (m, 1H), 2.09-2.17 (m, 1H), 2.30-2.40 (m, 1H), 3.39-3.58 (m, 3H), 3.60-3.64 (m, 1H), 3.64-3.73 (m, 1H), 4.18-4.22 (m, 1H), 4.24-4.32 (m, 1H), 5.23-5.38 (m, 2H), 6.94-6.98 (m, 1H), 7.05-7.10 (m, 1H), 7.16-7.20 (m, 1H), 7.26-7.35 (m, 1H), 7.38-7.46 (m, 5H); ESI-MS (M+H): 412.5; HPLC A: 1.79 min.

Provenance & Evidence