1,2-Dimethoxyethane → HCID 59251362, compound

HRID 1466424Notes

Reaction equation

HRID 1466424 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[C:11]([C:13]([OH:16])([CH3:15])[CH3:14])[N:10]=[C:9]2[C:17]2[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=2[F:24])=[CH:4][CH:3]=1.[CH3:25][S:26]([C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=1)(=[O:28])=[O:27].C(=O)([O-])[O-].[K+].[K+].COCCOC>[Pd].O>[F:24][C:18]1[CH:19]=[CH:20][CH:21]=[C:22]([F:23])[C:17]=1[C:9]1[N:8]([C:5]2[CH:6]=[CH:7][C:2]([C:33]3[CH:32]=[CH:31][CH:30]=[C:29]([S:26]([CH3:25])(=[O:28])=[O:27])[CH:34]=3)=[CH:3][CH:4]=2)[CH:12]=[C:11]([C:13]([OH:16])([CH3:15])[CH3:14])[N:10]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 27735423-(Methylsulfonyl)phenylboronic acidHCID 59251269HCID 59251269, compound

Product 1

HCID 59251362HCID 59251362, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

2-[1-(4-Bromo-phenyl)-2-(2,6-difluoro-phenyl)-1H-imidazol-4-yl]-propan-2-ol (250 mg, 0.64 mmol), (3-methylsulfonylphenyl)boronic acid (254 mg, 1.27 mmol), and potassium carbonate (398 mg, 2.88 mmol) were placed into a flask. 6 mL, of mixture of DME (1,2-dimethoxyethane) and water (9:1, V/V) was added. The flask was flushed with argon for 15 min, and then Pd catalyst (Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct, 52 mg, 0.064 mmol) was added. The mixture was heated to 80° C. overnight. After cooling to room temperature, all solvent was removed. The crude product was purified by column chromatography on silica gel (45→99% EtOAc/Hexane) to give an off-white solid (230 mg, 77% yield). 1H-NMR (400 MHz, CDCl3): δ 1.70 (s, 6H), 2.71 (s, 1H), 3.09 (s, 3H), 6.92-6.88 (m, 2H), 7.21 (s, 1H), 7.39-7.28 (m, 3H), 7.59-7.57 (m, 2H), 7.66 (t, 1H, J=7.8), 7.86-7.83 (M, 1H), 7.95-7.92 (m, 1H), 8.12 (t, 1H, J=1.7). MS (ES): 491.4 [M+Na]+

Workup

  1. additionwas added
  2. customThe flask was flushed with argon for 15 min
  3. temperatureAfter cooling to room temperature
  4. customall solvent was removed
  5. customThe crude product was purified by column chromatography on silica gel (45→99% EtOAc/Hexane)

Sources & evidence

ORD record
ord-9d9229656e184a3093b15ded1ec5548b
Source dataset
uspto-grants-2015_04
Patent number
US09000022B2

Reaction notes

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