Hexaethylene Glycol → HCID 11783358, compound

Temperature

20 °C

Mesyl chloride (1.78 mL, 23.0 mmol) was added dropwise to a stirred suspension of hexaethylene glycol (5.42 g, 19.2 mmol) and Ag2O (4.67 g, 20.2 mmol) in dry DCM (50 mL) at 20° C. and the mixture was stirred at 20° C. for 3 days. The mixture was filtered through Celite® and the solvent evaporated. The residue was purified by column chromatography, eluting with a gradient (0-10%) of MeOH/EtOAc, to give 17-hydroxy-3,6,9,12,15-pentaoxaheptadec-1-yl methanesulfonate (3.52 g, 51%) as a colourless oil: 1H NMR (CDCl3) δ 4.36-4.40 (m, 2H, CH2OSO2), 3.76-3.78 (m, 2H, CH2O), 3.70-3.74 (m, 2H, CH2O), 3.64-3.67 (m, 16H, 8×CH2O), 3.59-3.62 (m, 2H, CH2O), 3.09 (s, 3H, SO2CH3), 2.80 (br s, 1H, OH); MS m/z 361.6 (MH+, 100%). A mixture of the mesylate (3.52 g, 9.8 mmol) and NaN3 (1.27 g, 19.5 mmol) in dry DMF (20 mL) was stirred at 110° C. for 2 h. The mixture was cooled to 20° C. and the solvent evaporated. The residue was purified by column chromatography, eluting with 10% MeOH/EtOAc, to give 17-azido-3,6,9,12,15-pentaoxaheptadecan-1-ol (2.98 g, 99%) as a colourless oil: 1H NMR (CDCl3) δ3.71-3.74 (m, 2H, CH2O), 3.65-3.69 (m, 18H, 9×CH2O), 3.59-3.62 (m, 2H, CH2O), 3.39 (br t, J=5.2 Hz, 2H, CH2N3), 2.82 (br s, 1H, OH); MS m/z 308.5 (MH+, 100%). A mixture of azide (2.98 g, 9.7 mmol) and Pd/C (100 mg) in EtOH (50 mL) was stirred under H2 (60 psi) for 1 h. The mixture was filtered through Celite® and washed with EtOH (3×20 mL) and the solvent was evaporated. The crude residue was dissolved in DCM (50 mL) and di-tert-butyl dicarbonate (2.56 g, 11.7 mmol) in DCM (20 mL) was added dropwise and the solution was stirred at 20° C. for 16 h. The solvent was evaporated and residue was purified by column chromatography, eluting with 10% MeOH/EtOAc, to give tert-butyl 17-hydroxy-3,6,9,12,15-pentaoxaheptadec-1-ylcarbamate (2.97 g, 80%) as a colourless oil: 1H NMR (CDCl3) δ 5.17 (br s, 1H, NHCO2), 3.70-3.74 (m, 2H, CH2O), 3.60-3.68 (m, 18H, 9×CH2O), 3.54 (br t, J=5.1 Hz, 2H, CH2O), 3.31 (br q, J=5.1 Hz, 2H, CH2N), 2.81 (br s, 1H, OH), 1.44 [s, 9H, C(CH3)3]; MS m/z 382.5

1. filtrationThe mixture was filtered through Celite®
2. customthe solvent evaporated
3. customThe residue was purified by column chromatography
4. washeluting with a gradient (0-10%) of MeOH/EtOAc

ORD record

ord-e7a2d6fae3f6410d92804efd543907b9

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09296732B2