Sodium hydride → HCID 58970767, compound

HRID 1163077Notes

Reaction equation

HRID 1163077 reaction equation
[H-].[Na+].[F:3][C:4]([F:19])([F:18])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][C:9]=1[N+:15]([O-:17])=[O:16])=[O:6].[CH3:20][O:21][C:22](=[O:31])[C:23]1[CH:28]=[CH:27][C:26]([CH2:29]Br)=[CH:25][CH:24]=1>CCCCCC.CN(C=O)C>[CH3:20][O:21][C:22](=[O:31])[C:23]1[CH:28]=[CH:27][C:26]([CH2:29][N:7]([C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][C:9]=2[N+:15]([O-:17])=[O:16])[C:5](=[O:6])[C:4]([F:18])([F:19])[F:3])=[CH:25][CH:24]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 256687Methyl 4-(bromomethyl)benzoateHCID 4199254HCID 4199254, compound

Product 1

HCID 58970767HCID 58970767, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 8058HexaneSolvent

Procedure

A portion of 60% NaH in mineral oil (2.9 g, 71.8 mmol, 1.1 eq) was pre-washed with hexane and suspended in dry DMF under nitrogen. The slurry was cooled in an ice bath and a solution of 2,2,2-trifluoro-N-(4-methyl-2-nitrophenyl)-acetamide (16.2 g, 65.3 mmol, 1.0 eq) in dry DMF was added dropwise over 15 min. The cooling bath was removed and the mixture was stirred for 30 min. The reaction mixture was cooled again and a solution of 4-bromomethylbenzoic acid methyl ester (20 g, 65.3 mmol, 1.0 eq) in dry DMF was added dropwise over 10 min. The reaction mixture was stirred at room temperature for 18 h and evaporated under reduced pressure to give a residue. The residue was partitioned between ethyl acetate and water. The organic layer was washed sequentially with water and brine, dried (Na2SO4) and concentrated to give a yellow solid. The yellow solid was purified by column chromatography. (Silica gel 230-400 mesh: eluent CHCl3 MeOH:0→5%) to give 4-{[(4-methyl-2-nitrophenyl)-(2,2,2-trifluoroacetyl)amino]methyl}benzoic acid methyl ester, yield: 59%. 1H NMR (400 MHz, CDCl3): 7.97 (m, 3H); 7.27 (m, 3H); 6.76 (d, J=8 Hz, 1H); 5.66 & 4.26(2H); 3.92 (s, 3H); 2.46(s, 3H).

Workup

  1. temperatureThe slurry was cooled in an ice bath
  2. customThe cooling bath was removed
  3. temperatureThe reaction mixture was cooled again
  4. stirringThe reaction mixture was stirred at room temperature for 18 h
  5. customevaporated under reduced pressure
  6. customto give a residue
  7. customThe residue was partitioned between ethyl acetate and water
  8. washThe organic layer was washed sequentially with water and brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated
  11. customto give a yellow solid
  12. customThe yellow solid was purified by column chromatography

Sources & evidence

ORD record
ord-be167e4a521141d5838d1a5f1e25720b
Source dataset
uspto-grants-2010_10
Patent number
US07820825B2

Reaction notes

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