Ammonium Chloride → (S)-1-(2-fluorophenyl)-2-((1,1,1-trifluorobut-3-en-2-yl)oxy)ethanone

HRID 1429608노트

반응식

HRID 1429608 반응식
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[F:13].CON(C)[C:17](=[O:27])[CH2:18][O:19][C@@H:20]([CH:25]=[CH2:26])[C:21]([F:24])([F:23])[F:22].[NH4+].[Cl-]>CCCCCC.C1COCC1.[Cl-].[Na+].O>[F:13][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=1[C:17](=[O:27])[CH2:18][O:19][C@@H:20]([CH:25]=[CH2:26])[C:21]([F:23])([F:22])[F:24]

참가 물질

8

반응물 4

HCID 25517Ammonium ChlorideHCID 612591-Bromo-2-fluorobenzeneHCID 86668361(S)-N-Methoxy-N-methyl-2-((1,1,1-trifluorobut-3-en-2-yl)oxy)acetamideHCID 178418339Butyllithium

생성물 1

HCID 69936486(S)-1-(2-fluorophenyl)-2-((1,1,1-trifluorobut-3-en-2-yl)oxy)ethanone수율 72.8%

시약·촉매·용매 3

HCID 8028Tetrahydrofuran용매2회HCID 8058Hexane용매HCID 57417360Sodium chloride; water용매

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온도
-60 °C

실험 절차

A solution of n-butyllithium in hexane (2.50 M; 90 mL) was added dropwise over 25 mins to a solution of 2-bromofluorobenzene (40.35 g) in THF (250 mL) under a N2 atmosphere at −78° C. The reaction solution was allowed to warm to −60° C. and stir for 60 min. (S)—N-Methoxy-N-methyl-2-((1,1,1-trifluorobut-3-en-2-yl)oxy)acetamide (40 g) in THF (25 mL) was added dropwise to the reaction solution, and after stirring at −60° C. for 2 h, aqueous NH4Cl (100 mL) was added to the reaction solution, followed by warming to RT. Brine (200 mL) was added to the reaction solution, and the mixture was extracted with EtOAc (3×400 mL). The combined organic portions were dried over MgSO4, evaporated, and the residue was purified by silica gel column chromatography (1% to 10% EtOAc in hexanes) to obtain the title compound (33.59 g). 1H-NMR (400 MHz, CDCl3) δ (ppm): 4.40 (pentet, J 6.3 Hz, 1 H) 4.81-4.87 (m, 2 H), 5.54-5.69 (m, 2 H), 5.86 (ddd, J 17.4, 10.4, 7.3 Hz, 1 H) 7.12-7.22 (m, 1 H) 7.24-7.34 (m, 1 H) 7.54-7.63 (m, 1 H) 7.94-8.02 (m, 1 H).

후처리

  1. additionwas added dropwise to the reaction solution
  2. temperatureby warming to RT
  3. extractionthe mixture was extracted with EtOAc (3×400 mL)
  4. dry with materialThe combined organic portions were dried over MgSO4
  5. customevaporated
  6. customthe residue was purified by silica gel column chromatography (1% to 10% EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-11744bb704334363b21871067f7d1f53
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940734B2

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