Dabco → HCID 118274963、化合物

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レコード

ord-42c716e7ea4048248bef4fe9ce7b465b

出典データセット

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09266886B2