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

HRID 1849512ノート

反応式

HRID 1849512 の反応式
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

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 867028541-((4-Bromo-2-chloro-5-fluorobenzyl)oxy)adamantane

生成物 1

HCID 867028554-((adamantan-1-yloxy)methyl)-5-chloro-2-fluoro-N-(methylsulfonyl)benzamide収率 160.3%

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

反応条件

温度
100 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-d422218478684d76a84f98a5693e02fc
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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