4,4-Difluoro-1-methylcyclohexan-1-ol → 1-Bromo-5-chloro-4-(((4,4-difluoro-1-methylcyclohexyl)-oxy)methyl)-2-fluorobenzene

HRID 1849602Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1849602
ClC(Cl)(Cl)C(=N)O[CH2:5][C:6]1[CH:11]=[C:10]([F:12])[C:9]([Br:13])=[CH:8][C:7]=1[Cl:14].[F:18][C:19]1([F:27])[CH2:24][CH2:23][C:22]([CH3:26])([OH:25])[CH2:21][CH2:20]1>C(Cl)Cl.C1CCCCC1.FC(F)(F)S(O)(=O)=O>[Br:13][C:9]1[CH:8]=[C:7]([Cl:14])[C:6]([CH2:5][O:25][C:22]2([CH3:26])[CH2:23][CH2:24][C:19]([F:27])([F:18])[CH2:20][CH2:21]2)=[CH:11][C:10]=1[F:12]

Komponenten

6

Edukt 2

HCID 666026184,4-Difluoro-1-methylcyclohexan-1-olHCID 867028534-Bromo-2-chloro-5-fluorobenzyl 2,2,2-trichloroacetimidate

Produkt 1

HCID 867034571-Bromo-5-chloro-4-(((4,4-difluoro-1-methylcyclohexyl)-oxy)methyl)-2-fluorobenzeneAusbeute 18,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 62406Trifluoromethanesulfonic acidKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 8078CyclohexaneLösungsmittel

Versuchsvorschrift

To a solution of 4-bromo-2-chloro-5-fluorobenzyl 2,2,2-trichloroacetimidate (4.00 g, 10.40 mmol) and 4,4-difluoro-1-methylcyclohexanol (1.21 g, 8.05 mmol) in methylene chloride (50 mL) and cyclohexane (25 mL) was added trifluoromethanesulfonic acid (0.1 mL, 0.14 mmol) at 0 ?C. The reaction mixture was stirred for 56 hours at ambient temperature and quenched by addition of saturated sodium bicarbonate solution (10 mL), and then diluted with methylene chloride (100 mL). The organic layer was separated and washed with brine; dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by column chromatography (5% ethyl acetate in hexanes) and recrystallization from methanol afforded the title compound (0.54 g, 17%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ 7.51 (d, J=6.0 Hz, 1H), 7.30 (d, J=9.3 Hz, 1H), 4.37 (s, 2H), 2.11-1.86 (m, 6H), 1.72-1.59 (m, 2H), 1.26 (s, 3H).

Aufarbeitung

  1. customquenched by addition of saturated sodium bicarbonate solution (10 mL)
  2. additiondiluted with methylene chloride (100 mL)
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue
  8. customby column chromatography (5% ethyl acetate in hexanes) and recrystallization from methanol

Quellen und Nachweise

ORD-Eintrag
ord-746fd5b2a4b54983a61ed4921830cb89
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08952169B2

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