Ethylene Glycol → HCID 10999869, compound

Temperature

-78 °C

Dry DMSO (19.36 mL, 273.6 mmol) in dry CH2Cl2 (35 mL) was added dropwise to a stirred solution of 2 M (COCl)2 (68.40 mL, 136.8 mmol) at −78° C. during 15 min. The alcohol 12 (24 g, 109.44 mmol), prepared according to Example 11 , in dry dichloromethane (50 mL) was then added during 10 min, resulting in a slightly cloudy solution. This was stirred for 30 min at −78° C. and a solution of triethyl amine (79 mL, 547.2 mmol) in dichloromethane (50 mL) was then added dropwise during 15 min. The mixture was stirred for 30 min at −78° C. and 30 min at 0° C. The reaction was quenched by adding water (25 mL) with rapid stirring. The resulting slurry was immediately poured into ether (300 mL) and washed with 20% KHSO4 (2×200 mL). The layers were separated and the aqueous layer was extracted with ether (2×100 mL). The combined organic layers were washed with brine solution (2×100 mL), dried over MgSO4, filtered, and concentrated to afford crude aldehyde 13 (22 g) which was immediately used for protection. A stirred solution of crude 13 (22 g, 101.25 mmol), ethylene glycol (9.4 g, 151.87 mmol), and p-toluenesulfonic acid monohydrate (1 g) in dry benzene (200 mL), contained in a 500 mL round-bottom flask fitted with a Dean Stark trap, was heated at reflux for 12 h. The mixture was cooled to room temperature, the benzene layer was separated, and the aqueous layer was extracted with ether (2×100 mL). The combined organic layers were dried over MgSO4 and filtered. The residue obtained on concentration was purified by column chromatography on silica gel, using ether/hexane (1:1) as eluant, to give acetal 14 (21 g, 73.5%) as an oil. IR (KBr) νmax 3066, 3030, 2927, 2881, 1642, 1457, 1400, 1365, 1208, 1156, 1100, 1028, 946, 739, 628 cm−1; 1HNMR (CDCl3) δ 1.62-1.66 (m, 1 H), 1.79-1.91 (m, 2 H), 2.08-2.11 (m, 1 H), 2.25-2.28 (m, 1 H), 3.54 (t, J=6.9 Hz, 2 H), 3.78-3.90 (m, 4 H), 4.47 (s, 2 H), 4.80 (d, J=3.8 Hz, 1 H), 4.97-5.04 (m, 2 H), 5.77-5.82 (m, 1 H), 7.23-7.34 (m, 5 H); 13CNMR (CDCl3) δ 28.55, 33.78, 38.33, 64.77, 64.86, 68.40, 72.59, 106.00, 116.04, 127.29, 127.45, 128.16, 136.66, 138.62; mass spectrum (EI), m/z (rel intensity) 262 (M+. 1.6), 171 (4.4), 156 (3.2), 149 (9), 128 (3.3), 114 (2.6), 109 (7), 105 (4.1), 99 (3.6), 92 (3.7), 91 (31), 81 (3.7), 77 (5), 73 (100), 67 (4), 65 (6).

1. additionwas then added during 10 min
2. customresulting in a slightly cloudy solution
3. stirringThe mixture was stirred for 30 min at −78° C. and 30 min at 0° C
4. customThe reaction was quenched
5. additionby adding water (25 mL) with rapid stirring
6. additionThe resulting slurry was immediately poured into ether (300 mL)
7. washwashed with 20% KHSO4 (2×200 mL)
8. customThe layers were separated
9. extractionthe aqueous layer was extracted with ether (2×100 mL)
10. washThe combined organic layers were washed with brine solution (2×100 mL)
11. dry with materialdried over MgSO4
12. filtrationfiltered
13. concentrationconcentrated
14. customto afford crude aldehyde 13 (22 g) which
15. customfitted with a Dean Stark trap
16. temperaturewas heated
17. temperatureat reflux for 12 h
18. temperatureThe mixture was cooled to room temperature
19. customthe benzene layer was separated
20. extractionthe aqueous layer was extracted with ether (2×100 mL)
21. dry with materialThe combined organic layers were dried over MgSO4
22. filtrationfiltered
23. customThe residue obtained on concentration
24. customwas purified by column chromatography on silica gel

ORD record

ord-7aeb76e180d6484b9e9424c0628c246e

Source dataset

uspto-grants-2001_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06211360B1