Methyl iodide → HCID 22414475, compound

HRID 486686Notes

Reaction equation

HRID 486686 reaction equation
[CH3:1][C:2]([CH3:17])([CH3:16])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][CH:7]=1)=[O:4].O1CCC[CH2:19]1.[Li+].CCC[CH2-].IC>CCCCCC.O>[CH3:1][C:2]([CH3:17])([CH3:16])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]([F:13])([F:14])[F:15])=[CH:8][C:7]=1[CH3:19])=[O:4]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 8028TetrahydrofuranHCID 61028n-Butyl lithiumHCID 2774289N-(4-(trifluoromethyl)phenyl)pivalamide

Product 1

HCID 22414475HCID 22414475, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8058HexaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a chilled (28° C.) solution of 4.91 g of 2,2-dimethyl-N-(4-trifluoromethylphenyl)propanamide and 80 ml tetrahydrofuran, was added over two mins, 18.5 ml of a 2.5M solution of N-butyllithium in hexane, with stirring. The reaction mixture was stirred for two hours at 0° C. and added, dropwise over eight minutes, to a solution of 3.19 g of iodomethane and 7 ml of hexane, keeping the temperature between -2° C.+1° C. The solution was stirred for 45 mins (internal temperature reached 18° C.). Water (20 ml) was added and the mixture was extracted with dichloromethane. The combined organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated. The mixture was separated by preparative HPLC (Waters Associates Prep LC/System 500, silica gel, sample applied in and eluted with methylenechloride, 200 ml/min flow rate). The appropriate fractions were combined, concentrated, and the residue was recrystallized from toluene to give 2.23 g of product, mp 111°-114° C.

Workup

  1. additionwas added over two mins
  2. custombetween -2° C.
  3. custom1° C
  4. stirringThe solution was stirred for 45 mins (internal temperature reached 18° C.)
  5. extractionthe mixture was extracted with dichloromethane
  6. dry with materialThe combined organic phase was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe mixture was separated by preparative HPLC (Waters Associates Prep LC/System 500, silica gel, sample applied in and eluted with methylenechloride, 200 ml/min flow rate)
  10. concentrationconcentrated
  11. customthe residue was recrystallized from toluene

Sources & evidence

ORD record
ord-1ca7b91f0d1d48819fc8b8f8e23f19d1
Source dataset
uspto-grants-1994_03
Patent number
US05292760

Reaction notes

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