Cyclohexanone → HCID 10352983, compound

Temperature

-78 °C

According to Scheme 26 Step 1: To a stirred solution of 4-bromo-2-methoxypyridine (1 eq, 5.30 mmol, 1.00 g) in anhydrous THF (30 mL) at −78° C. under nitrogen was added dropwise a solution of butyl lithium (1.3 eq, 2.5M solution in hexane, 6.90 mmol, 2.8 mL). The reaction was then stirred at −78° C. for 2 hours. Cyclohexanone (5 eq, 27.0 mmol, 2.8 mL) was then added dropwise over 5 minutes. The reaction was stirred at −78° C. for two hours then allowed to warm to room temperature. The reaction was stirred for a further 16 hours then quenched with water. The reaction was evaporated in vacuo, redissolved in CH2Cl2 (100 mL) and washed with brine (100 mL). The organic phase was extracted, dried over MgSO4, filtered and evaporated to leave a yellow oil. The oil was purified by column chromatography (AIT Flashsmart prepacked column 25 g SiO2, pure AcOEt), yielding the title compound (4.10 mmol, 0.86 g, 78%) as a colorless oil which solidified on standing.

1. stirringThe reaction was stirred at −78° C. for two hours
2. temperatureto warm to room temperature
3. stirringThe reaction was stirred for a further 16 hours
4. customthen quenched with water
5. customThe reaction was evaporated in vacuo
6. dissolutionredissolved in CH2Cl2 (100 mL)
7. washwashed with brine (100 mL)
8. extractionThe organic phase was extracted
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. customevaporated
12. customto leave a yellow oil
13. customThe oil was purified by column chromatography (AIT Flashsmart prepacked column 25 g SiO2, pure AcOEt)

ORD record

ord-12f7a5372e364238b155468dbbaafd45

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399493B2