Dabco → HCID 118274963, Verbindung

To a mixture of ethyl(S)-4-((tert-butoxycarbonyl)amino)-5-methyl-3-oxohexanoate (9.68 g, 33.7 mmol) from above in THF (100 mL) at 0° C. was added potassium tert-butoxide (3.78 g, 35.4 mmol). The mixture was warmed to rt and stirred for 45 min, at which point 1,4-diazabicyclo[2.2.2]octane (3.78 g, 33.7 mmol) and 2-chloro-1,3-bis(dimethylamino)trimethinium hexaflurophosphate (15.5 g, 50.5 mmol) were added successively. The mixture was heated to 45° C. and stirred for 3 h, at which point ammonium acetate (5.19 g, 67.4 mmol) was added. The mixture was then heated to reflux and stirred for 15 h. It was then cooled to rt and concentrated under reduced pressure. The residue was dry-loaded onto a silica gel column and purified (eluting with 5% EtOAc in hexanes, gradient to 15%) to yield 6.09 g of ethyl(S)-2-(1-((tert-butoxycarbonyl)amino)-2-methylpropyl)-5-chloronicotinate (51%). LC-MS tR=1.14 min in 1 min chromatography, MS (ESI) m/z 357.3 [M+H]+. 1H NMR (CDCl3, 400 MHz): δ 8.61 (d, J=2.4 Hz, 1H), 8.18 (d, J=2.8 Hz, 1H), 5.71 (d, J=9.6 Hz, 1H), 5.62 (dd, J=5.2 Hz, 9.6 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 2.08-2.00 (m, 1H), 1.42 (s, 9H), 1.42 (t, J=7.2 Hz, 3H), 0.93 (d, J=6.4 Hz, 3H), 0.83 (d, J=6.4 Hz, 3H).

1. additionwere added successively
2. temperatureThe mixture was heated to 45° C.
3. additionwas added
4. temperatureThe mixture was then heated
5. temperatureto reflux
6. temperatureIt was then cooled to rt
7. concentrationconcentrated under reduced pressure
8. custompurified
9. wash(eluting with 5% EtOAc in hexanes, gradient to 15%)

ORD-Eintrag

ord-42c716e7ea4048248bef4fe9ce7b465b

Quelldatensatz

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09266886B2