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

HRID 1849603노트

반응식

HRID 1849603 반응식
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]

참가 물질

10

반응물 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

생성물 1

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

시약·촉매·용매 5

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

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-49ad231c20f1409caed12bc9ccd09e08
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08952169B2

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