Diisopropylethylamine → HCID 57453594, compound

Participants

Reaction Conditions

Reaction Steps

A 200 mL round-bottomed flask was charged with (3R,5S)-5-(methoxycarbonyl)pyrrolidin-3-yl 4-chloroisoindoline-2-carboxylate hydrochloride (1.20 g, 3.32 mmol), (S)-2-(tert-butoxycarbonyl)-3,3-dimethylbutanoic acid (807 mg, 3.49 mmol) and HATU (1.90 g, 4.98 mmol) in dry MeCN (30 mL). The solution was then cooled on an ethanol-ice bath and treated with DIEA (1.74 mL, 9.97 mmol) by dropwise addition. The mixture was stirred at 0° C. for 1 h, then allowed to warm up and stirred at room temperature for 16 h. The mixture was then concentrated and the residue dissolved in EtOAc (100 mL) and washed with iced 5% citric acid (aq.) (3×30 mL), 1M NaOH (3×30 mL), water (3×30 mL) and brine (3×30 mL). The organic layer was dried over MgSO4, filtered and concentrated to an oil. The oil was purified by chromatography (Biotage) eluting with 35% EtOAc-hexanes to give the product as a white foam, 1.27 g, 71%. MS m/e 438 (M+H)+−Boc. 1H NMR (400 MHz, d6-DMSO) δ 7.3-7.4 (m, 3H), 6.7-6.76 (m, 1H), 5.24 (bs, 1H), 4.4-4.76 (m, 4H), 4.12-4.2 (m, 1H), 3.96-4.3 (m, 1H), 3.7-3.78 (m, 1H), 3.64 (d, 3H), 2.38-2.48 (m, 1H), 2.07-2.16 (m, 1H), 1.14 (d, 9H), 0.98 (s, 9H).

Provenance & Evidence