Acetic Acid → HCID 87545026, compound

HRID 2067940Notes

Reaction equation

HRID 2067940 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[Cl:11][C:12]1[CH:17]=[C:16]([CH3:18])[CH:15]=[CH:14][N:13]=1.COCN[C:23]([C:25]1[C:29]([CH3:30])=[C:28]([C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=2)[N:27]([CH3:38])[N:26]=1)=[O:24].C(O)(=O)C>C1COCC1>[Cl:11][C:12]1[CH:17]=[C:16]([CH2:18][C:23]([C:25]2[C:29]([CH3:30])=[C:28]([C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=3)[N:27]([CH3:38])[N:26]=2)=[O:24])[CH:15]=[CH:14][N:13]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 772482-Chloro-4-methylpyridineHCID 2724254Sodium bis(trimethylsilyl)amideHCID 68709955HCID 68709955, compound

Product 1

HCID 87545026HCID 87545026, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
-70 °C

Procedure

To 10 ml of dry THF cooled to −65° C. were added 1.35 ml of a 2M solution of Sodium-bis(trimethylsilyl)amide in THF. Then a solution of 0.32 g 2-Chlor-4-methyl pyridine in 1 ml of dry THF was added dropwise maintaining the temperature at −70° C. for 30 min. Then a solution of 0.50 g of 5-(4-Fluoro-phenyl)-1,4-dimethyl-1H-pyrazole-3-carboxylic acid methoxymethyl-amide in 5 ml of dry THF was added dropwise over a 10 min period maintaining the temperature below −65° C. The solution was stirred for 2 h at −60° C., and then allowed to warm up to 0° C. and stirred for 20 min at this temperature. Then 0.31 ml of Acetic acid was added dropwise at −50° C., and the solution was allowed to warm up to room temperature and stirred overnight. The mixture was concentrated in vaccuo. The residue was taken up in Ethyl acetate. The organic phase was washed with saturated bicarbonate solution and brine, dried over magnesium sulfate, filtered and evaporated. The crude product (0.67 g, yellow oil) was purified by chromatography on silica gel (Heptane/Ethyl acetate 4:1). The desired product was obtained as a white solid (0.27 g, 70%), MS: m/e=344.0 ([M+1]+).

Workup

  1. temperaturemaintaining the temperature below −65° C
  2. temperatureto warm up to 0° C.
  3. stirringstirred for 20 min at this temperature
  4. temperatureto warm up to room temperature
  5. stirringstirred overnight
  6. concentrationThe mixture was concentrated in vaccuo
  7. washThe organic phase was washed with saturated bicarbonate solution and brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. customevaporated
  11. customThe crude product (0.67 g, yellow oil) was purified by chromatography on silica gel (Heptane/Ethyl acetate 4:1)

Sources & evidence

ORD record
ord-81c7194e53ab4a75a2f5b1c36c1c9981
Source dataset
uspto-grants-2012_10
Patent number
US08293916B2

Reaction notes

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