Dimethyl Carbonate → HCID 46942028, compound

Temperature

0 °C

A solution of LDA (2M in THF/heptane/ethyl benzene, 44 ml, 88 mmol) was added dropwise to a stirred solution of 4-methyl-2-[4-(trifluoromethyl)phenyl]pyridine (10.5 g, 44 mmol) in dry THF (300 ml) under N2, such that the internal temperature remained <−70° C. After 1 hour at this temperature, dimethyl carbonate (8.9 ml, 106 mmol) was added. After 30 minutes the cooling bath was removed. When the internal temperature had reached −20° C. the reaction was transferred to a cold bath at −10° C., and then allowed to warm slowly to 0° C. After 1 hour at 0° C. the reaction was quenched with aqueous NH4Cl (half saturated, 100 ml). The reaction mixture was concentrated in vacuo. The residue was diluted with H2O (200 ml) and extracted with EtOAc (2×200 ml). The combined extracts were washed with brine (×1), then dried (MgSO4), filtered and evaporated. The residue was purified by chromatography on silica, eluting with 10-30% EtOAc/isohexane to give the ester (9.2 g, 71%) as a pale yellow liquid. 1H NMR (400 MHz, CDCl3) δ: 3.72 (2H, s), 3.75 (3H, s), 7.24 (1H, dd, J 1.4, 5.0), 7.72 (3H, t, J 8.4), 8.11 (2H, d, J 8.2), 8.68 (1H, d, J 5.0).

1. customremained <−70° C
2. customAfter 30 minutes the cooling bath was removed
3. customhad reached −20° C.
4. customwas transferred to a cold bath at −10° C.
5. customAfter 1 hour at 0° C. the reaction was quenched with aqueous NH4Cl (half saturated, 100 ml)
6. concentrationThe reaction mixture was concentrated in vacuo
7. additionThe residue was diluted with H2O (200 ml)
8. extractionextracted with EtOAc (2×200 ml)
9. washThe combined extracts were washed with brine (×1)
10. dry with materialdried (MgSO4)
11. filtrationfiltered
12. customevaporated
13. customThe residue was purified by chromatography on silica
14. washeluting with 10-30% EtOAc/isohexane

ORD record

ord-cb6a8522919343f78d02bf6c19e5d47f

Source dataset

uspto-grants-2011_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07985758B2