Diisopropylamine → Methyl{2-[4-(trifluoromethyl)phenyl]pyridin-3-yl}acetate

Temperature

0 °C

A solution of diisopropylamine (4.8 ml, 34 mmol) in dry THF (20 ml) was cooled to 0° C. and n-butyllithium (1.6M in hexanes, 21.3 ml, 34 mmol) was added dropwise. After stirring at 0° C. for 30 mins, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (4.1 ml, 34 mmol) was added. After 15 mins a solution of the pyridine (Step 1, 4.033 g, 17 mmol) in dry THF (10 ml) was added. The reaction was stirred for 15 mins at 0° C. then cooled to −78° C. and dimethyl carbonate (3.4 ml, 40 mmol) in dry THF (10 ml) was added. The reaction was allowed to warm to −5° C. and stirred for 1 hr then quenched with saturated NH4Cl solution. The mixture was extracted with EtOAc (×3), the combined extracts were washed with brine, dried (MgSO4), filtered and evaporated. The residue was purified by chromatography (silica, 10-30% EtOAc/hexanes) to give the ester (0.621 g, 12%). 1H NMR (500 MHz, CDCl3) δ: 3.65 (2H, s), 3.67 (3H, s), 7.31-7.34 (1H, m), 7.61-7.62 (2H, m), 7.71-7.75 (3H, m), 8.63-8.64 (1H, m).

1. stirringThe reaction was stirred for 15 mins at 0° C.
2. temperaturethen cooled to −78° C.
3. temperatureto warm to −5° C.
4. stirringstirred for 1 hr
5. customthen quenched with saturated NH4Cl solution
6. extractionThe mixture was extracted with EtOAc (×3)
7. washthe combined extracts were washed with brine
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. customevaporated
11. customThe residue was purified by chromatography (silica, 10-30% EtOAc/hexanes)

ORD record

ord-6eef45274a8441258042bbf0d0286dd2

Source dataset

uspto-grants-2009_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07638629B2