Diisopropylethylamine → HCID 21904440, compound

Participants

Reaction Steps

Protocol for preparing the diester phosphoramidite diethyl 5-[[[[bis(1-methylethyl)amino](2-cyanoethoxy)phosphino]oxy]methyl]-1,3-benzenedicarboxylate: 1.29 g (5 mmol) of diethyl 5-(hydroxymethyl)isophthalate [252.27] (98%, Aldrich; CAS 181425-91-2) were dissolved in 20 ml of dry dichloromethane at room temperature and mixed with 2.59 g (40 mmol, 4 eq) of N-ethyldiisopropylamine [129.25] and 1.3 g (11 mmol, 1.1 eq) of 2-cyanoethyl N,N-diisopropylchlorophosphoramidite [236.68] (Aldrich; CAS 89992-70-1). After 15 min at room temperature, thin layer chromatography (ethyl acetate/n-heptane (1:4) showed completion of the reaction. The mixture was concentrated and mixed with 30 ml of ethyl acetate/n-heptane (2:3). The precipitated hydrochloride was removed by filtration. The filtrate was concentrated and applied directly to a chromatography column. Elution with ethyl acetate/n-heptane (1:4) gave 1.6 g (70%) of diethyl 5-[[[[bis(1-methylethyl)amino](2-cyanoethoxy)phosphino]oxy]methyl]-1,3-benzenedicarboxylate as a colorless oil. C22H33N2O6P; 1H-NMR 8.59 (m, 1H, arom.), 8.21 (m, 2H, arom.), 4.87-4.75 (m, 2H, CH2 cyanoethyl), 4.41 (q, J=6.98 Hz, 4H, CH2 ethyl), 3.95-3.80 (m, 2H, 2×CH i-Pr), 3.74-3.61 (m, 2H, CH2 cyanoethyl), 2.66 (t, J (P,H)=6.45 Hz, 2H, O—CH2-arom), 1.41 (t, J=6H, 2×CH3 ethyl), 1.23-1.20 (m, 12H, CH3, i-Pr): 31P-NMR (CDCl3): δ 149.94; 13C-NMR (CDCl3): δ=165.8 (C═O), 140.2 (C—CH2—O—P), 132.1 (2×C arom.), 131.1 (2×C—H arom), 129.7 (C H arom), 117.6 (CN), 64.7 (P—O—CH2-arom), 61.4 (2×CH2 ethyl), 58.6 (O—CH2—CH2—CN), 43.4 (2×C—H i-Pr), 24.7 (4×CH3 i-Pr), 20.5 (O—CH2—CH2—CN), 14.4 (CH3 ethyl); HRMS 453.2156 ([M+H]+C22H34N2O6P calculated: 453.21545). Chromatographic purification and analytical characterization were carried out according to the protocols described above.

Provenance & Evidence