Methyl iodide → Dicyclohexylammonium (RS)-alpha-Methyl-3,5-bis(trifluoromethyl)benzeneacetate

HRID 2213002Notes

Reaction equation

HRID 2213002 reaction equation
[CH2:1]([Li])CCC.[F:6][C:7]([F:23])([F:22])[C:8]1[CH:9]=[C:10]([CH2:18][C:19]([OH:21])=[O:20])[CH:11]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:13]=1.IC.S(=O)(O)[O-].[Na+].[CH:31]1([NH:37][CH:38]2[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]2)[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1>O1CCCC1>[CH3:1][CH:18]([C:10]1[CH:9]=[C:8]([C:7]([F:22])([F:23])[F:6])[CH:13]=[C:12]([C:14]([F:16])([F:17])[F:15])[CH:11]=1)[C:19]([O-:21])=[O:20].[CH:38]1([NH2+:37][CH:31]2[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]2)[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43]1

Participants

7

Reactant 5

HCID 6328Methyl iodideHCID 7582DicyclohexylamineHCID 1235873,5-Bis(trifluoromethyl)phenylacetic acidHCID 23665763Sodium BisulfiteHCID 178418339Butyllithium

Product 1

HCID 86590571Dicyclohexylammonium (RS)-alpha-Methyl-3,5-bis(trifluoromethyl)benzeneacetateYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

n-Butyllithium (2.5M solution in hexanes, 67.6 mL, 169 mmol) was added slowly to a stirred, cooled (−78° C.) solution of 3,5-bis(trifluoromethyl)benzeneacetic acid (20.0 g, 73.5 mmol) in tetrahydrofuran (400 mL) and the mixture was stirred at −78° C. for 1 hour. Iodomethane (6.87 mL, 110 mmol) was added slowly and the mixture was allowed to warm to room temperature and stirred overnight. Aqueous sodium bisulfite (20%) was added until the mixture was acidic. The mixture was extracted with ethyl acetate, the combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate (400 mL), dicyclohexylamine (10 mL, 80.85 mmol) was added and the mixture was heated under reflux for 1 hour. The mixture was cooled and the solid was collected and dried in vacuo to give the title compound as a colorless solid (31.13 g, 91%). 1H NMR (400 MHz, CDCl3) δ 7.83 (2H, s), 7.68 (1H, s), 3.66 (1H, q, J 7.1 Hz), 2.83–2.75 (2H, m), 1.87–1.84 (4H, m), 1.71–1.68 (4H, m), 1.60–1.57 (2H, m), 1.48 (3H, d, J 7.1 Hz), 1.28–1.08 (8H, m), and 1.03–0.92 (2H, m).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred overnight
  3. extractionThe mixture was extracted with ethyl acetate
  4. dry with materialthe combined organic fractions were dried (MgSO4)
  5. customthe solvent was evaporated under reduced pressure
  6. dissolutionThe residue was dissolved in ethyl acetate (400 mL)
  7. temperaturethe mixture was heated
  8. temperatureunder reflux for 1 hour
  9. temperatureThe mixture was cooled
  10. customthe solid was collected
  11. customdried in vacuo

Sources & evidence

ORD record
ord-f45ac49a55804b42a26a7eb5545e78bb
Source dataset
uspto-grants-2006_09
Patent number
US07105507B2

Reaction notes

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