Dimethyl Carbonate → [2-(4-Fluoro-phenyl)-6-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-acetic acid methyl ester

HRID 2427872Notes

Reaction equation

HRID 2427872 reaction equation
[Li+].CC([N-]C(C)C)C.[F:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[C:20]([CH3:22])[CH:19]=[C:18]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=3)[N:17]=2)=[CH:12][CH:11]=1.[C:33](=O)([O:36]C)[O:34][CH3:35]>>[CH3:35][O:34][C:33](=[O:36])[CH2:22][C:20]1[CH:19]=[C:18]([C:23]2[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:30])[F:31])=[CH:25][CH:24]=2)[N:17]=[C:16]([C:13]2[CH:12]=[CH:11][C:10]([F:9])=[CH:15][CH:14]=2)[CH:21]=1

Participants

4

Reactant 3

HCID 12021Dimethyl CarbonateHCID 2724682Lithium diisopropylamideHCID 591617312-(4-Fluoro-phenyl)-4-methyl-6-(4-trifluoromethyl-phenyl)-pyridine

Product 1

HCID 59161733[2-(4-Fluoro-phenyl)-6-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-acetic acid methyl esterYield 42%

Conditions

Temperature
-78 °C

Procedure

A solution of LDA (1.8 M in THF/heptane/ethyl benzene, 1.1 mL, 2.0 mmol) was added slowly to a stirred solution of 2-(4-fluoro-phenyl)-4-methyl-6-(4-trifluoromethyl-phenyl)-pyridine (260 g, 0.8 mmol) under N2 at −78° C. After 30 minutes dimethyl carbonate (200 μL, 2.0 mmol) was added. After stirring at −78° C. for an additional 30 minutes, the solution was allowed to warm slowly and stirred at 0° C. for 30 minutes. The reaction was quenched with saturated aqueous NH4Cl (2 mL). The mixture was partitioned between CH2Cl2 and H2O. The aqueous layer was extracted with CH2Cl2 (2×). The combined extracts were washed with brine, then dried (Na2SO4), filtered and evaporated. The residue was purified by column chromatography on silica gel (40-80% CH2Cl2 in heptane) to give the product as a white solid (130 mg, 42%). 1H NMR (300 MHz, CDCl3) δ 8.23 (d, J=7.91 Hz, 2H), 8.13 (dd, J=5.46, 8.85 Hz, 2H), 7.75 (d, J=8.29 Hz, 2H), 7.64 (d, J=2.64 Hz, 2H), 7.19 (t, J=8.67 Hz, 2H), 3.78 (s, 2H), 3.76 (s, 3H). MS m/e 390.2 (M+H).

Workup

  1. temperatureto warm slowly
  2. stirringstirred at 0° C. for 30 minutes
  3. customThe reaction was quenched with saturated aqueous NH4Cl (2 mL)
  4. customThe mixture was partitioned between CH2Cl2 and H2O
  5. extractionThe aqueous layer was extracted with CH2Cl2 (2×)
  6. washThe combined extracts were washed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by column chromatography on silica gel (40-80% CH2Cl2 in heptane)

Sources & evidence

ORD record
ord-3897b2e0915445de85c76edebb10e0dc
Source dataset
uspto-grants-2011_06
Patent number
US07968725B2

Reaction notes

Loading…