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

HRID 2213002
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HRID 2213002 반응식
[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
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7

반응물 5

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
-78 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-f45ac49a55804b42a26a7eb5545e78bb
출처 데이터셋
uspto-grants-2006_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07105507B2

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