Triethyl phosphite → HCID 11065603, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of CuI (83.64 g, 437.0 mmol) in dry THF (875 mL), vinylmagnesium chloride (1.9 M in THF, 460.0 mL, 874.0 mmol) is added under argon atmosphere at 44 to −31° C. in 15 minutes under vigorous stirring. The resulting dark slurry is stirred for 15 minutes, and DMPU (112 g, 874.0 mmol) is added at 42° C. in one portion followed by the dropwise addition (5 minutes) of P(OEt)3 (160.1 mL, 874.0 mmol) at 40° C. The resulting mixture is stirred for 30 minutes and a THF (220 mL) solution of (S)-ethyl 3-(tert-butyldimethylsilyloxy)-4-iodobutyrate (3) (162.7 g, 437.0 mmol) is added at −40 to −36° C. in 15 minutes. The stirring is continued for 1 hour at −40 to −35° C. before allowing the mixture to warm to 11° C. over a period of 3.5 hours. The reaction is quenched at −2° C. (saturated NH4Cl, 1.0 L) and stirred at 10° C. for 30 minutes. The product is extracted with i-Pr2O or t-BuMeO. Partial evaporation of the solvent under reduced pressure gives a yellow solution which is washed with 0.1 M H2SO4, water and dried (MgSO4). Ether is removed completely under reduced pressure (15 mbar) at 80° C. to produce a yellow oily residue. This residue is purified further by vacuum distillation (64-72° C. at 0.10-0.44 mbar) to give 80.8 g (67.8%) of ethyl 3(R)-(tert-butyldimethylsilyloxy)-5-hexenoate (4) as a colorless oil (GC purity 96%). 1H NMR (300 MHz, CDCl3): δ 5.81 (ddt, J=17.8, 9.6 and 7.2 Hz, 1H), 5.11-5.03 (m, 2H), 4.21 (quint., J=6.8 Hz, 1H), 4.12 (qt, J=7.1 and 1.5 Hz, 2H), 2.43 (d, J=7.1 Hz, 1H), 2.43 (d, J=5.4 Hz, 1H), 2.31−2.25 (m, 2H), 1.26 (t, J=7.2 Hz, 3H), 0.87 (s, 9H), 0.07 (s, 3H), 0.04 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 171.7, 134.1, 117.6, 68.9, 60.2, 42.1, 42.1, 25.7, 17.9, 14.1, −4.6, −5.0.

Provenance & Evidence