Pentamethyldiethylenetriamine → HCID 67372137, compound

To a solution of 1-ethoxy-3,5-difluoro-benzene (7.50 g, 47.42 mmol, 1.0 equiv) and N-(2-dimethylamino-ethyl)-N,N′,N′-trimethyl-ethane-1,2-diamine (8.63 g, 10.40 mL, 49.80 mmol, 1.05 equiv) in anhydrous THF (125 mL) was added n-BuLi (31.13 mL, 49.80 mmol, 1.05 equiv; 1.6 M solution in hexane) within 1 h at −100° C. A solution of glyoxylic acid ethyl ester (9.68 g, 94.85 mmol, 2.0 equiv) in toluene (19 mL) was slowly added over a time period of 45 min and stirring continued for 2 h at −100° C. The cooling bath was removed and at −30° C. a solution of 2 M HCl (105 mL) was added. The solution was concentrated by evaporation under reduced pressure and the reaction mixture extracted with ethyl acetate (3×100 mL). The combined organic phases were dried over MgSO4 and concentrated by evaporation under reduced pressure. The crude material was purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane/ethyl acetate to give 8.2 g (66%) of the title compound. 1H NMR (300 MHz, CDCl3): 1.24 (t, J=7.5 Hz, 3H), 1.41 (t, J=7.5 Hz, 3H), 3.47 (d, J=6.0 Hz, 1H), 4.00 (q, J=7.5 Hz, 2H), 4.28 (q, J=7.5 Hz, 2H), 5.38 (d, J=6.0 Hz, 1H), 6.41-6.47 (m, 2H).

1. customThe cooling bath was removed and at −30° C. a solution of 2 M HCl (105 mL)
2. additionwas added
3. concentrationThe solution was concentrated by evaporation under reduced pressure
4. extractionthe reaction mixture extracted with ethyl acetate (3×100 mL)
5. dry with materialThe combined organic phases were dried over MgSO4
6. concentrationconcentrated by evaporation under reduced pressure
7. customThe crude material was purified by silica column chromatography
8. washeluting with a gradient of heptane/ethyl acetate

ORD record

ord-0cdd928560cd4836aee597d1411257be

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08008503B2