Pentane → HCID 86268842, compound

Participants

Reaction Conditions

Reaction Steps

Compound 8 (0.48 kg) and NFSI (N-fluorobenzenesulfonimide) (0.29 kg) was dissolved in THF (3 L) and ether (1 L). To the solution was added 1.5 L of n-pentane, and the mixture was cooled to −78° C. in a dry-ice bath. A solution of n-BuLi in THF (2.5 M, 0.72 L) was added drop wise to the reaction mixture within 4 hours, while keeping the reaction temperature below −70° C. The reaction mixture was stirred another hour until HPLC indicated complete consumption of compound 8. Saturated ammonium chloride solution (aqueous, 2 L) was added drop wise to the reaction mixture. It was then allowed to warm to ambient temperature. Eight such reactions were combined and diluted with 30 L of ethyl acetate. The mixture was stirred for 30 minutes, then the organic phase separated and the aqueous layer was extracted with 20 L of ethyl acetate. The combined organic phase was washed with brine (10 L), dried over sodium sulfate, and concentrated to dryness. HPLC indicated ratio of compound 9 to its corresponding de-fluoro side product was about 3/1. The residue was loaded on a silica gel column (300˜400 mesh) and eluted with petroleum ether/dichloromethane/ethyl acetate (first 100/0/0, then 200/10/1 to remove the front impurities, then changed to 200/15/1 to collect the desired product 9, (then 200/20/1 to collect the side product). Altogether 1.38 kg of compound 9 (yield 36%, purity˜95%) was obtained. 1H-NMR (300 MHz, CDCl3) δ 7.25-7.92 (m, 25H), 5.04 (t, J=7.2 Hz, 1H), 4.45 (m, 1H), 4.33 (m, 1H), 3.98 (d, J=12.0 Hz, 1H), 3.86 (d, J=12.0 Hz, 1H), 1.55 (s, 3H), 1.48 (s, 3H), 1.18 (s, 9H); 13C-NMR DEPT-135 (75 MHz, CDCl3, δ<100) δ 78.70, 75.35, 71.10, 56.39, 28.04, 27.25, 26.82.

Provenance & Evidence