Urea → HCID 9923121, compound

Participants

Reaction Steps

To a solution of 27B (500 mg, 1.83 mmol) in CH2Cl2 (1.5 mL) was added TFA (1.5 mL). The reaction mixture was stirred at RT for 1 h, then concentrated under reduced pressure to give an oily residue, which was stripped with toluene (3×) and dried in vacuo overnight. The oily residue was dissolved in CH2Cl2 (10 mL) and to the solution was added N,N-diisopropylethylamine (0.35 mL, 2.01 mmol), followed by a solution of 6B (355 mg, 1.83 mmol) in CH2Cl2 (5 mL) and 4 Å molecular sieves (1 g). The reaction mixture was stirred at RT for 1 h, the resulting turbid solution (formation of the urea intermediate) was treated with DBU (0.41 mL, 2.745 mmol), and stirred at RT for an additional 1 h. The clear reaction solution was partitioned between CH2Cl2 and 5% aqueous KHSO4. The aqueous phase was extracted with CH2Cl2 (2×) and the combined CH2Cl2 extracts were washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated under reduced pressure to give a crude product, which was chromatographed (silica gel) eluting with 4% MeOH in EtOAc/hexane (1:1) to give 330 mg of the desired product as a racemic mixture. The title compound (8 mg) was isolated by using preparative HPLC with a chiral column (CHIRALPAK® AD, 5×50 cm, 20μ) and 10% of isopropanol/hexane as an eluate. Chiral HPLC: 99% at 20.6 min (retention time) (CHIRALPAK® AD column 4.6×250 mm; 20% isopropanol in hexane over 30 minutes, 1 mL/min, monitoring at 220 nM); MS (ES): m/z 322 [M+1]+.

Provenance & Evidence