Cyclopentanol → Cyclopentyl chloroformate

Cyclopentanol (0.431 mL, 4.75 mmol, 17.4 equiv) was dissolved in dry CH2Cl2 (25 mL). Triethylamine (0.662 mL, 4.75 mmol, 17.4 equiv) and triphosgene (0.507 g, 1.71 mmol, 6.26 equiv) were added sequentially. The reaction solution was stirred 2.5 hours to provide a stock solution of cyclopentyl chloroformate (0.19 M). A portion of this solution (2.87 mL, 0.545 mmol, 2 equiv) was added to a solution of crude ethyl-3-[H2N-L-ValΨ[COCH2]-L-(p-F)Phe-L-(Tr-Gln)]-E-propenoate•HCl (from above) and 4-methylmorpholine (0.120 mL, 1.09 mmol, 4 equiv) in dry CH2Cl2 (4 mL). The reaction mixture was stirred for 1.75 hours, then poured into water (30 mL), and extracted with CH2Cl2 (3×30 mL). The combined organic phases were dried over Na2SO4, concentrated, and the residue was chromatographed on silica gel (gradient elution 40→50% EtOAc in hexanes) to afford ethyl-3-[CyPentylOCO-L-ValΨ[COCH2]-L-(p-F)Phe-L-(Tr-Gln)]-E-propenoate (0.077 g, 35%) as a colorless glass: 1H NMR (CDCl3) δ 0.68 (d, 3H, J=6.8), 0.93 (d, 3H, J=6.8), 1.29 (t, 3H, J=7.2), 1.50-1.86 (m, 10H), 1.93-2.04 (m, 21), 2.29-2.38 (m, 2H), 2.52 (d, 1H, J=15.9), 2.64 (dd, 1H, J=12.1, 5.6), 2.73-2.90 (m, 2H), 2.99 (dd, 1H, J=17.0, 9.8), 4.10-4.22 (m, 3H), 4.40-4.51 (m, 1H), 4.92 (d, 1H, J=8.1), 4.95-5.03 (m, 1H), 5.38 (d, 1H, J=15.9), 6.06 (d, 1H, J=8.4), 6.60 (dd, 1H, J=15.9, 4.8), 6.92-7.00 (m, 2H), 7.04-7.11 (m, 2H), 7.16-7.32 (m, 15H).

ORD record

ord-352f3d231dc34d5ba286d5886e1de70c

Source dataset

uspto-grants-2003_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06649639B2