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

HRID 1849603ノート

反応式

HRID 1849603 の反応式
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]

参加物

10

反応物 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

生成物 1

HCID 867034585-chloro-4-(((4,4-difluoro-1-methylcyclohexyl)-oxy)methyl)-2-fluoro-N-(methylsulfonyl)benzamide収率 161.1%

試薬・触媒・溶媒 5

HCID 98885Molybdenum carbonyl (Mo(CO)6)触媒HCID 167845palladium(II) acetate触媒HCID 6344Dichloromethane溶媒HCID 25517Ammonium Chloride溶媒HCID 312751,4-Dioxane溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-49ad231c20f1409caed12bc9ccd09e08
出典データセット
uspto-grants-2015_02
特許番号
US08952169B2

反応ノート

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