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

HRID 1849603Notes

Reaction equation

HRID 1849603 reaction equation
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]

Participants

10

Reactant 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

Product 1

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

Reagents, catalysts & solvents 5

HCID 98885Molybdenum carbonyl (Mo(CO)6)CatalystHCID 167845palladium(II) acetateCatalystHCID 6344DichloromethaneSolventHCID 25517Ammonium ChlorideSolventHCID 312751,4-DioxaneSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-49ad231c20f1409caed12bc9ccd09e08
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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