Diethyl Carbonate → 9-Iodo-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione

Temperature

-78 °C

(Z)-ethyl 2-(5-iodo-3,4-dihydroisoquinolin-1(2H)-ylidene)acetate. To a yellow cooled solution of 5-iodo-1-methyl-3,4-dihydroisoquinoline (30.1 g, 111 mmol) in dry THF (900 mL) was added dropwise a solution of LDA (2M in THF, 111 mL, 222 mmol) at −78° C. The resulting brown solution was stirred for at −78° C. for 45 min and a solution of diethyl carbonate (14 mL, 116 mmol) in THF (80 mL) was then added dropwise. The mixture was stirred at −78° C. for another 45 min, and then poured onto brine. The resulting yellow suspension was filtered and the filter cake was washed with AcOEt. The filtrate was extracted with AcOEt, and the combined org. phases were dried over Na2SO4, filtered and concentrated in vacuo to give the title compound (40.0 g) as a brown oil that was used as it is in the next step. UPLC-MS: MS 344.1 (M+H+); UPLC rt 1.28 min.

1. stirringThe mixture was stirred at −78° C. for another 45 min
2. additionpoured onto brine
3. filtrationThe resulting yellow suspension was filtered
4. washthe filter cake was washed with AcOEt
5. extractionThe filtrate was extracted with AcOEt
6. dry with materialphases were dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo

ORD record

ord-79416e36ee694eff92505151ed95eb57

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09284331B2