N-methoxy-N-methyl-2-phenylamino-6-trifluoromethyl-nicotinamide → 1-(2-Phenylamino-6-trifluoromethyl-pyridin-3-yl)-propan-1-one

HRID 1887820Notes

Reaction equation

HRID 1887820 reaction equation
CON(C)[C:4](=[O:22])[C:5]1[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[N:7][C:6]=1[NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[CH2:24]([Mg]Br)[CH3:25]>C1COCC1>[C:16]1([NH:15][C:6]2[C:5]([C:4](=[O:22])[CH2:24][CH3:25])=[CH:10][CH:9]=[C:8]([C:11]([F:12])([F:13])[F:14])[N:7]=2)[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

4

Reactant 2

HCID 86672055N-methoxy-N-methyl-2-phenylamino-6-trifluoromethyl-nicotinamideHCID 178418443HCID 178418443, compound2×

Product 1

HCID 712085931-(2-Phenylamino-6-trifluoromethyl-pyridin-3-yl)-propan-1-oneYield 86.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

In a 250 mL round-bottomed flask, N-methoxy-N-methyl-2-phenylamino-6-trifluoromethyl-nicotinamide (1.73 g, 5.32 mmol) was combined with THF (20 mL) to give a brown solution and the solution was cooled to 0° C. Ethylmagnesium bromide (1.0 M in THF) (16 mL, 16.0 mmol) was added dropwise at 0° C. over 5 min. The reaction mixture was stirred in an ice bath for 2.5 hr and 1 hr at room temperature. Additional ethylmagnesium bromide (1.0 M in THF) (6 mL, 6.00 mmol) was introduced over 3 min and the mixture was stirred for 2 hr at room temperature. The reaction mixture was cautiously quenched with water (50 mL) and extracted with ethyl acetate (3×50 mL). The organic layers were combined, washed with brine (1×50 mL), dried over MgSO4 and concentrated in vacuo to give 1.56 g of crude product as a yellow solid. The crude material was purified by flash chromatography (silica gel, 150 g, 15% ethyl acetate in hexanes) to give 1-(2-phenylamino-6-trifluoromethyl-pyridin-3-yl)-propan-1-one (1.35 g, 86.3% yield) as a yellow solid. 1H NMR (DMSO-d6) δ ppm 11.13 (s, 7H) 8.67 (d, J=8.2 Hz, 1H) 7.74 (d, J=7.8 Hz, 2H) 7.20-7.54 (m, 3H) 6.81-7.19 (m, 1H) 3.19 (q, J=7.2 Hz, 2H) 1.12 (t, J=7.1 Hz, 3H). MS calcd. for C15H13F3N2O [(M+H)+] 295.0, obsd. 295.0.

Workup

  1. customto give a brown solution
  2. stirringthe mixture was stirred for 2 hr at room temperature
  3. customThe reaction mixture was cautiously quenched with water (50 mL)
  4. extractionextracted with ethyl acetate (3×50 mL)
  5. washwashed with brine (1×50 mL)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customto give 1.56 g of crude product as a yellow solid
  9. customThe crude material was purified by flash chromatography (silica gel, 150 g, 15% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-ad65f613975441f7b3ecd212ab950d4b
Source dataset
uspto-grants-2013_08
Patent number
US08501732B2

Reaction notes

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