Iodine → HCID 69557648, compound

Temperature

-78 °C

To a solution of 500 mg (1.43 mmol) 4-(tert-butyl-dimethyl-silanyloxy)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-carboxylic acid methylamide, 1.7 ml (11 mmol) N,N,N′,N′-tetramethyl-ethylenediamine and 1.0 ml (5.7 mmol) 2,2,6,6-tetramethylpiperidine in 9.5 ml dry tetrahydrofuran 7.2 ml (11 mmol) of a 1.6 M solution of n-butyllithium in hexanes were added dropwise during 10 min. at −78° C. under argon. The resulting solution was stirred at −78° C. for 30 min., warmed to −20° C. and stirred at this temperature for 3 h. After cooling the reaction mixture to −78° C. a solution of 2.92 g (11.5 mmol) iodine in 7 ml dry tetrahydrofuran was added dropwise under argon. The resulting suspension was kept at −78° C. for 2 h and subsequently allowed to warm to room temperature over 1 h. The suspension was poured into a solution of 12.4 g (50.0 mmol) sodium thiosulfate pentahydrate in 50 ml ice-water. The resulting yellow suspension was extracted with two 250-ml portions of tert-butyl methyl ether. The combined organic extracts were washed with 2 portions of a saturated aqueous ammonium chloride solution, dried with sodium sulfate and concentrated. Flash chromatography afforded 495 mg (72.8 %) of the title compound as an off-white amorphous mass.

1. temperaturewarmed to −20° C.
2. stirringstirred at this temperature for 3 h
3. additionwas added dropwise under argon
4. waitThe resulting suspension was kept at −78° C. for 2 h
5. temperatureto warm to room temperature over 1 h
6. extractionThe resulting yellow suspension was extracted with two 250-ml portions of tert-butyl methyl ether
7. washThe combined organic extracts were washed with 2 portions of a saturated aqueous ammonium chloride solution
8. dry with materialdried with sodium sulfate
9. concentrationconcentrated

ORD record

ord-78281d64785042ea92476bbe6a41c0ce

Source dataset

uspto-grants-2003_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06576762B2