Toluene → HCID 178456375, compound

HRID 1984040Notes

Reaction equation

HRID 1984040 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH:9]2[CH2:14][CH2:13][CH:12]([C:15]([N:17]3[CH2:22][CH2:21][N:20]([CH:23]([CH3:25])[CH3:24])[CH2:19][CH2:18]3)=[O:16])[CH2:11][CH2:10]2)=[N:6][CH:7]=1.[F:26][C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][C:32]=1[F:33].C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[F:26][C:27]1[CH:28]=[C:29]([C:2]2[CH:3]=[CH:4][C:5]([O:8][C@H:9]3[CH2:14][CH2:13][C@H:12]([C:15]([N:17]4[CH2:22][CH2:21][N:20]([CH:23]([CH3:25])[CH3:24])[CH2:19][CH2:18]4)=[O:16])[CH2:11][CH2:10]3)=[N:6][CH:7]=2)[CH:30]=[CH:31][C:32]=1[F:33]

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27343373,4-Difluorobenzeneboronic acidHCID 25125026HCID 25125026, compound

Product 1

HCID 178456375HCID 178456375, compoundYield 17.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 120 mg (0.29 mmol) of [4-(5-bromo-pyridin-2-yloxy)-cyclohexyl]-(4-isopropyl-piperazin-1-yl)-methanone, 69 mg (0.44 mmol) of 3,4-difluorophenylboronic acid, 34 mg (0.03 mmol) of tetrakis(triphenylphosphine)palladium, and 93 mg (0.88 mmol) of sodium carbonate, 1.5 ml of toluene and 0.5 ml of water was refluxed for 5 hr under Ar. The mixture was diluted with AcOEt, washed with saturated NaHCO3 solution and brine, dried over MgSO4, and evaporated. The residue was purified by column chromatography on silica eluting with cyclohexane and ethyl acetate=from 100:0 to 4:1. The combined product fractions were evaporated to dryness to yield 22 mg (17%) of the title compound. MS (m/e): 444.2 (MH+).

Workup

  1. temperaturewas refluxed for 5 hr under Ar
  2. washwashed with saturated NaHCO3 solution and brine
  3. dry with materialdried over MgSO4
  4. customevaporated
  5. customThe residue was purified by column chromatography on silica eluting with cyclohexane and ethyl acetate=from 100:0 to 4:1
  6. customThe combined product fractions were evaporated to dryness

Sources & evidence

ORD record
ord-0ed452243ba14488aef1bda8aa008ab9
Source dataset
uspto-grants-2009_06
Patent number
US07544683B2

Reaction notes

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