Diethyl Ether → Bis(2-(trimethylsilyl)ethyl) diisopropylphosphoramidite

Temperature

-1 °C

A solution of diisopropylphosphoramidous dichloride (10.8 g 50.78 mmoles) in Et2O (53 mL) in 250 mL three neck flask equipped with a temperature probe and addition funnel was cooled to 0 to −2° C. under N2. A solution of 2-(trimethylsilyl)ethanol (12.6 g; 106.55 mmoles) and Et3N (15.4 g; 152.19 mmoles) in Et2O (84 mL) was added dropwise over 27-28 minutes to the stirred diisopropyl-phosphoramidous dichloride solution. A mild exotherm (+1-2° C.) accompanied the formation of a thick white suspension. After stirring overnight at 20° C., the mixture was filtered. The resultant cake was washed twice with 30 mL each of Et2O. The combined filtrates were washed 2×100 mL of saturated aqueous NaHCO3 followed by 40 mL of brine. After drying over MgSO4 and concentrating to dryness under vacuum at room temperature, bis(2-(trimethylsilyl)ethyl) diisopropylphosphoramidite (18.12 g; 49.56 mmoles; 97.60% yield) was obtained as a clear colorless liquid. 1H NMR δ (400 MHz, CDCl3): 3.90-3.78 (m, 4H), 3.77-3.68 (m, 2H), 1.31 (d, J=6.6 Hz, 12H), 1.17-1.12 (m, 4H), 0.15 (s, 18H). 13C NMR δ (100 MHz, CDCl3): δ0.7 (2, d, JC—P=19.1 Hz, 2C), 42.7 (1, d, JC—P=12.7 Hz, 2C), 24.6 (3, d, JC—P=7.6 Hz, 4C), 20.1 (2, d, JC—P=7.6 Hz, 2C), −1.4 (3, 6C). 31P NMR δ (162 MHz, CDCl3): 143.5 (s). LC/MS: m/e (M+H); 4 ml gradient; min retention.

1. customA mild exotherm (+1-2° C.)
2. filtrationthe mixture was filtered
3. washThe resultant cake was washed twice with 30 mL each of Et2O
4. washThe combined filtrates were washed 2×100 mL of saturated aqueous NaHCO3
5. dry with materialAfter drying over MgSO4
6. concentrationconcentrating to dryness under vacuum at room temperature

ORD record

ord-a1db452801ec40de9d5f7edec971c0a6

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07989433B2