Dichloromethane → HCID 68698106, compound

Temperature

-78 °C

A solution of 1,4-dibromobenzene (2.29 g, 9.72 mmol, 1.9 eq) in THF (20 ml) under N2 was cooled to −78° C., and n-butyllithium (1.6 M in hexanes, 4.8 ml, 7.67 mmol, 1.5 eq) was added dropwise. The reaction mixture was stirred at −78° C. for 40 minutes, and a solution of N-methoxy-N-methyl-1-(pyrimidin-2-yl)piperadine-4-carboxamide (1.28 g, 5.11 mmol, 1 eq) in THF (5 ml) was added dropwise via a cannula. After 3 hours at −78° C., the reaction mixture was warmed to 0° C., stirred for 1 hour, and then quenched with 1 N aq. HCl (10 ml). The mixture was diluted with 150 ml of ethyl acetate, washed sequentially with saturated aq. NaHCO3 and brine (75 ml each), and the organic phase was dried over Na2SO4 and concentrated. Column chromatography (silica gel, CH2Cl2 3.5% ethyl acetate/CH2Cl2) afforded 1.47 g (83% yield) of the product as a pale yellow solid: HPLC: 99% pure at 3.748 min (YMC-Pack ODS-A 4.6×33 mm column, 0% 100% solvent B over 4 min, 3 ml/min, 220 nm); LCMS (M+H)+=345.90; 400 MHz 1H NMR (CDCl3) 8.31 (d, J=4.7 Hz, 2H), 7.83 (d, J=8.5 Hz, 2H), 7.63 (d, J=8.5 Hz, 2H), 6.48 (t, J=4.7 Hz, 1H), 4.81 (m, 2H), 3.49 (m, 1H), 3.08 (m, 2H), 1.72-1.95 (m, 4H).

1. waitAfter 3 hours at −78° C.
2. temperaturethe reaction mixture was warmed to 0° C.
3. stirringstirred for 1 hour
4. customquenched with 1 N aq. HCl (10 ml)
5. additionThe mixture was diluted with 150 ml of ethyl acetate
6. washwashed sequentially with saturated aq. NaHCO3 and brine (75 ml each)
7. dry with materialthe organic phase was dried over Na2SO4
8. concentrationconcentrated

ORD record

ord-621dc971072546d69d84c706ef0a5490

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772291B2