137348-86-8

Clear Colourless Liquid

A phosphinane derivative with immunomodulating activity.

reaction type: Buchwald-Hartwig Cross Coupling Reaction
reaction type: Heck Reaction
reaction type: Hiyama Coupling
reaction type: Negishi Coupling
reaction type: Sonogashira Coupling
reaction type: Stille Coupling
reaction type: Suzuki-Miyaura Coupling
reagent type: ligand

General procedure for the synthesis of di-tert-butyl N,N-diisopropylphosphoramidite from dichloro-N,N-diisopropylphosphoramidite and tert-butyl alcohol: tert-butyl alcohol (3.7 g, 4.7 mL, 50 mmol, 2.0 eq.) and triethylamine (5.6 g, 7.7 mL, 55 mmol, 2.2 eq.) were prepared under anhydrous conditions by dissolving them in anhydrous ether (20 mL) as a solution. This solution was slowly added to a solution of dichloro-N,N-diisopropylphosphoramidite (5.0 g, 25 mmol) in anhydrous ethyl ether (5 mL) while keeping the reaction temperature below 0°C. The reaction temperature was kept below 0°C for a few minutes. After the addition was complete (about 15 minutes), the reaction mixture was slowly warmed to room temperature and stirring was continued for 3 hours. Upon completion of the reaction, the aqueous phase was separated by adding 5% aqueous sodium bicarbonate solution (10 mL) for quenching. The organic phase was washed sequentially with 5% aqueous sodium bicarbonate (2 x 10 mL) and saturated aqueous sodium chloride (25 mL), then dried over anhydrous sodium sulfate, filtered and concentrated to give a clarified oily residue. The target product, N,N-diisopropylphosphoramidite di-tert-butyl ester, was purified by vacuum distillation as a clear oil (4.3 g, 63% yield). The boiling point of the product was 56-57 °C (0.05 mmHg).1H-NMR (300 MHz, CDCl3) δ 1.17 (d, J = 6.0 Hz, CH(CH3)2), 1.35 (s, 18H, 2 × C(CH3)3), 3.53-3.68 (m, 2 × CH(CH3)2); 13C-NMR (125 MHz, CDCl3) δ 24.5 (s, 18H, 3.53-3.68 (m, 2 × CH(CH3)2)); and 13C-NMR (125 MHz, CDCl3) δ 24.0 (m, 2 × C(CH3)3). CDCl3) δ 24.21 (d, JPC = 7.73 Hz), 31.06 (d, JPC = 9.75 Hz), 43.09 (d, JPC = 13.88 Hz), 74.50 (d, JPC = 9.75 Hz); 31P-NMR (202 MHz, CDCl3) δ 130.0 (s).

[1] Patent: US7018987, 2006, B1. Location in patent: Page/Page column 9
[2] Journal of the Chemical Society. Perkin Transactions 2, 1998, # 7, p. 1621 - 1628
[3] Phosphorus, Sulfur and Silicon and Related Elements, 2000, vol. 164, p. 277 - 291