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

HRID 1427831노트

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HRID 1427831 반응식
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

참가 물질

10

반응물 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

생성물 1

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

시약·촉매·용매 5

HCID 98885Molybdenum carbonyl (Mo(CO)6)촉매HCID 167845palladium(II) acetate촉매HCID 6344Dichloromethane용매HCID 25517Ammonium Chloride용매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-ff6956099d954afd824bca89fdb6778c
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08933236B2

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