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

HRID 2427876Notes

Reaction equation

HRID 2427876 reaction equation
[Li+].CC([N-]C(C)C)C.[Cl:9][C:10]1[CH:15]=[C:14]([CH3:16])[CH:13]=[C:12]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=2)[N:11]=1.[C:27](=O)([O:30]C)[O:28][CH3:29]>>[CH3:29][O:28][C:27](=[O:30])[CH2:16][C:14]1[CH:13]=[C:12]([C:17]2[CH:18]=[CH:19][C:20]([C:23]([F:24])([F:25])[F:26])=[CH:21][CH:22]=2)[N:11]=[C:10]([Cl:9])[CH:15]=1

Participants

4

Reactant 3

HCID 12021Dimethyl CarbonateHCID 2724682Lithium diisopropylamideHCID 574686282-Chloro-4-methyl-6-(4-trifluoromethyl-phenyl)-pyridine

Product 1

HCID 59161716[2-Chloro-6-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-acetic acid methyl esterYield 79%

Conditions

Temperature
-78 °C

Procedure

A solution of LDA (1.8 M in THF/heptane/ethyl benzene, 3.0 mL, 5.4 mmol) was added slowly to a stirred solution of 2-Chloro-4-methyl-6-(4-trifluoromethyl-phenyl)-pyridine (545 g, 2.0 mmol) under N2 at −78° C. After 30 minutes dimethyl carbonate (400 μL, 4.0 mmol) was added. After stirring at −78° C. for an additional 30 minutes, the solution was allowed to warm up slowly and stirred at 0° C. for 30 minutes. The reaction was quenched with saturated aqueous NH4Cl (4 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 an off white solid (520 mg, 79%). 1H NMR (300 MHz, CDCl3) δ 8.11 (d, J=8.29 Hz, 2H), 7.72 (d, J=8.29 Hz, 2H), 7.62 (s, 1H), 7.28 (s, 1H), 3.76 (s, 3H), 3.71 (s, 2H). MS m/e 330.1 (M+H).

Workup

  1. temperatureto warm up slowly
  2. stirringstirred at 0° C. for 30 minutes
  3. customThe reaction was quenched with saturated aqueous NH4Cl (4 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-fe34d3a0eeab497288a5b0656fd760cb
Source dataset
uspto-grants-2011_06
Patent number
US07968725B2

Reaction notes

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