Allyl bromide → Benzyl 2-allyl-2-hydroxycyclopentanecarboxylate

Participants

Reaction Steps

To a solution of benzyl 2-oxocyclopentanecarboxylate (from step A, 5 g, 22.91 mmol) in a mixture of methanol (20 ml) and water (60.00 ml) was added 3-bromoprop-1-ene (8.31 g, 68.7 mmol) and indium (1.081 ml, 68.7 mmol). The resulting mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated and to the residue was added 1N hydrogen chloride (15 mL) and stirred at room temperature for 5 min. The reaction mixture was partitioned between ethyl acetate (30 mL) and water (4 mL). The ethyl acetate layer is washed with brine (4 mL), dried over anhydrous Na2SO4 and concentrated under the reduced pressure. The residue was subjected to preparative HPLC (Shimadzu VP-ODS 20×100 mm, 8 min. gradient, Solvent A: 10% MeOH, 90% H2O, 0.1% TFA; Solvent B: 90% MeOH, 10% H2O, 0.1% TFA; wavelength: 220 nM). The desired fractions were collected, concentrated under reduced pressure to yield the desired product as a diastereomer mixture. The diastereomer mixture was subjected to chiral preparative HPLC to yield four individual isomers. The fractions corresponding to the second isomer was concentrated and freeze dried to yield a solid (800 mg, 3.08 mmol, 13.4% yield). Chiral HPLC method: Column: ChiralPak AD-H, 250×3 cm, 5 μm; Flow rate: 130 mL/min; Mobile Phase: CO2/MeOH=70/30; Inj. Vol.=0.7 mL, Wavelength=220 nM, :Retention time=3.18 min. MS (ESI+)=283 (M+Na)+

Provenance & Evidence