Triethylamine → 5-chloro-4-(((4,4-difluoro-1-methylcyclohexyl)-oxy)methyl)-2-fluoro-N-(methylsulfonyl)benzamide

HRID 1849603Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1849603
Br[C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([CH2:9][O:10][C:11]2([CH3:19])[CH2:16][CH2:15][C:14]([F:18])([F:17])[CH2:13][CH2:12]2)=[CH:4][C:3]=1[F:20].[CH3:21][S:22]([NH2:25])(=[O:24])=[O:23].C(N(CC)CC)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:54][C:36]2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C(Cl)Cl.[Cl-].[NH4+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:8][C:6]1[C:5]([CH2:9][O:10][C:11]2([CH3:19])[CH2:16][CH2:15][C:14]([F:18])([F:17])[CH2:13][CH2:12]2)=[CH:4][C:3]([F:20])=[C:2]([CH:7]=1)[C:36]([NH:25][S:22]([CH3:21])(=[O:24])=[O:23])=[O:54]

Komponenten

10

Edukt 4

HCID 8471TriethylamineHCID 72879MethanesulfonamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 867034571-Bromo-5-chloro-4-(((4,4-difluoro-1-methylcyclohexyl)-oxy)methyl)-2-fluorobenzene

Produkt 1

HCID 867034585-chloro-4-(((4,4-difluoro-1-methylcyclohexyl)-oxy)methyl)-2-fluoro-N-(methylsulfonyl)benzamideAusbeute 161,1 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 98885Molybdenum carbonyl (Mo(CO)6)KatalysatorHCID 167845palladium(II) acetateKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 25517Ammonium ChlorideLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A mixture of 1-bromo-5-chloro-4-(((4,4-difluoro-1-methylcyclohexyl)-oxy)methyl)-2-fluorobenzene (0.20 g, 0.50 mmol), methanesulfonamide (0.14 g, 1.50 mmol), molybdenumhexacarbonyl (0.13 g, 0.50 mmol) and triethylamine (0.3 mL, 2.15 mmol) in dioxane was sparged with nitrogen for 5 minutes, xantphos (0.05 g, 0.09 mmol) and palladium acetate (0.01 g, 0.045 mmol) were added to the reaction mixture. The reaction mixture was heated at 100 □C for 1 hour under microwave irradiation (300 psi) and then cooled to ambient temperature, diluted with methylene chloride (100 mL) and saturated ammonium chloride (20 mL). The organic layer was washed with brine; dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by column chromatography (10% to 30% gradient ethyl acetate in hexanes) afforded the title compound (0.06 g, 28%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ 8.78 (d, J=15.0 Hz, 1H), 8.05 (d, J=6.9 Hz, 1H), 7.42 (d, J=12.9 Hz, 1H), 4.47 (s, 2H), 3.42 (s, 3H), 2.11-1.89 (m, 6H), 1.74-1.62 (m, 2H), 1.27 (s, 3H); MS (ES−) m/z 412.1, 414.1 (M−1).

Aufarbeitung

  1. customwas sparged with nitrogen for 5 minutes
  2. temperatureThe reaction mixture was heated at 100 □C for 1 hour under microwave irradiation (300 psi)
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by column chromatography (10% to 30% gradient ethyl acetate in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-49ad231c20f1409caed12bc9ccd09e08
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08952169B2

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