Diisopropylethylamine → Boc-prolylproline methyl ester

Participants

Reaction Conditions

Reaction Steps

METHOD 2 N-tert-butoxycarbonyl L-proline (3.04 g, 14.1 mmol) and L-proline methyl ester hydrochloride (2.34 g, 14.1 mmol) were dissolved in CH2Cl2 (25 mL). N,N-diisopropylethylamine (1.82 g, 14.1 mmol) was added and the solution cooled to 0° C. (icebath). HOBt hydrate (2.16 g, 14.1 mmol) and then EDC hydrochloride (2.97 g, 15.5 mmol) were added together with 15 mL CH2Cl2. The icebath was removed and the reaction mixture stirred for 16 h 15 min at room temperature. The reaction mixture was diluted with CH2Cl2 (60 mL) and the solution washed with 1M HCl(3×25 mL), 7.5% (w/w) K2CO3 solution (3×25 mL) and saturated brine (25 mL). The solution was dried with anhydrous MgSO4 and the solvent evaporated affording the title compound as a very pale yellow, almost clear oil, which was dried under high vacuum overnight. The compound (3.67 g, 79%) showed spectral characteristics in accordance with published data1; δH (200 MHz; d6-DMSO) 4.56-4.31 (2H, m, CαH(Pro1)/CαH(Pro2)), 3.78-3.28 (4H, m, CδH2(Pro1)/CδH2(Pro2)), 3.67 (3H, s, OCH3, rotomer 1), 3.65 (3H, s, OCH3, rotomer 2), 2.26-1.65 (8H, m, CH2), 1.40/1.34/1.22 (9H, s, (CH3)3, all rotomers); δC (75 MHz; CDCl3) 172.8, 172.5, 171.5, 171.0, 154.4, 153.6, 79.3, 58.5, 57.6, 57.5, 53.3, 52.0, 51.9, 46.7, 46.5, 46.3, 29.8, 28.9, 28.7, 28.6, 28.3, 28.2, 24.9, 24.8, 23.9, 23.4

Provenance & Evidence