Methyl iodide → HCID 67253051, compound

HRID 383749Notes

Reaction equation

HRID 383749 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:9]([CH3:10])=[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[C:17]([F:20])([F:19])[F:18])[NH:7][CH:6]=1)=[O:4].[CH3:21][Si]([N-][Si](C)(C)C)(C)C.[Li+].IC>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[C:9]([CH3:10])=[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[C:17]([F:20])([F:19])[F:18])[N:7]([CH3:21])[CH:6]=1)=[O:4]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 67251895Methyl 4-methyl-5-(2-(trifluoromethyl)phenyl)-1H-pyrrole-3-carboxylate

Product 1

HCID 67253051HCID 67253051, compoundYield 92.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-methyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid methyl ester (2.9 g, 10.2 mmol) in anhyd THF (40 mL) was added lithium bis(trimethylsilyl)amide (1.0 M solution in THF, 12.3 mL, 12.3 mmol) slowly at 20° C. After stirring 0.5 h, iodomethane (0.96 mL, 15.4 mmol) was added and the mixture was stirred for 3 h at 20° C. After quenching with water, the organic layer was separated and the aqueous layer was extracted with EtOAc. The combined extracts were washed with water, dried (anhyd Na2SO4) and concentrated under reduced pressure to yield 1,4-dimethyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid methyl ester as an oil (2.8 g, 92%), which was used in the next step without purification. MS (ES): 298 (MH+). To a solution of 4-methyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid methyl ester (2.9 g, 10.2 mmol) in anhyd THF (40 mL) was added lithium bis(trimethylsilyl)amide C. To a solution of 1,4-dimethyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid methyl ester (2.5 g, 8.4 mmol) in MeOH (20 mL) was added 4N NaOH (10 mL) and the mixture was heated to reflux overnight. Evaporation of solvent gave a solid, which was re-dissolved in water. The solution was acidified with formic acid. The resulting solids were collected by filtration, washed with water and then dried under high vacuum to afford the title compound as an off-white solid (2.15 g, 90%). MS (ES): 284 (MH+).

Workup

  1. stirringthe mixture was stirred for 3 h at 20° C
  2. customAfter quenching with water
  3. customthe organic layer was separated
  4. extractionthe aqueous layer was extracted with EtOAc
  5. washThe combined extracts were washed with water
  6. dry with materialdried (anhyd Na2SO4)
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b72a712a1efc4b35a2da9e5ec6000747
Source dataset
uspto-grants-2013_02
Patent number
US08367667B2

Reaction notes

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