Triethylamine → 4-((adamantan-1-yloxy)methyl)-5-chloro-2-fluoro-N-(methylsulfonyl)benzamide

HRID 1427831Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1427831
Br[C:2]1[C:19]([F:20])=[CH:18][C:5]([CH2:6][O:7][C:8]23[CH2:17][CH:12]4[CH2:13][CH:14]([CH2:16][CH:10]([CH2:11]4)[CH2:9]2)[CH2:15]3)=[C:4]([Cl:21])[CH:3]=1.[CH3:22][S:23]([NH2:26])(=[O:25])=[O:24].C(N(CC)CC)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:55][C:37]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>[C:8]12([O:7][CH2:6][C:5]3[C:4]([Cl:21])=[CH:3][C:2]([C:37]([NH:26][S:23]([CH3:22])(=[O:25])=[O:24])=[O:55])=[C:19]([F:20])[CH:18]=3)[CH2:17][CH:12]3[CH2:13][CH:14]([CH2:16][CH:10]([CH2:11]3)[CH2:9]1)[CH2:15]2

Komponenten

10

Edukt 4

HCID 8471TriethylamineHCID 72879MethanesulfonamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 867028541-((4-Bromo-2-chloro-5-fluorobenzyl)oxy)adamantane

Produkt 1

HCID 867028554-((adamantan-1-yloxy)methyl)-5-chloro-2-fluoro-N-(methylsulfonyl)benzamideAusbeute 160,3 %

Reagenzien, Katalysatoren, Lösungsmittel 5

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

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of 1-((4-bromo-2-chloro-5-fluorobenzyl)oxy)adamantane (0.37 g, 1.00 mmol), methanesulfonamide (0.29 g, 3.00 mmol), molybdenumhexacarbonyl (0.27 g, 1.00 mmol) and triethylamine (0.6 mL, 4.30 mmol) in dioxane was purged with nitrogen for 5 min, xantphos (0.10 g, 0.18 mmol) and palladium acetate (0.02 g, 2.00 mmol) were added to the reaction mixture. The reaction mixture was heated at 100° C. for 1 h 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 as a colorless solid (0.12 g, 28%): 1H NMR (300 MHz, CDCl3) δ 8.74 (br s, 1H), 8.01 (d, J=6.9 Hz, 1H), 7.49 (d, J=12.9 Hz, 1H), 4.57 (s, 2H), 3.41 (s, 3H), 2.18 (br s, 3H), 1.84-1.81 (m, 6H), 1.70-1.54 (m, 6H); MS (ES−) m/z: 414.1, 416.1 (M−1).

Aufarbeitung

  1. customwas purged with nitrogen for 5 min
  2. temperaturecooled to ambient temperature
  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-ff6956099d954afd824bca89fdb6778c
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08933236B2

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