Dichloromethane → 3-(2-methoxyphenyl)-1-perhydro-2H-pyran-2-yl-1H-indazole-5-carbonitrile

HRID 1349658Notes

Reaction equation

HRID 1349658 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[N:4]([CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][O:14]2)[N:3]=1.[CH3:19][O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1B(O)O.ClCCl.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:19][O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[N:4]([CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][O:14]2)[N:3]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 27339582-Methoxyphenylboronic acidHCID 224799453-Bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carbonitrile

Product 1

HCID 224801423-(2-methoxyphenyl)-1-perhydro-2H-pyran-2-yl-1H-indazole-5-carbonitrileYield 82.5%

Reagents, catalysts & solvents 2

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of 3-bromo-1-perhydro-2H-pyran-2-yl-1H-indazole-5-carbonitrile (0.600 g, 1.96 mmol), in ethylene glycol dimethyl ether (20 mL) was added 2-methoxyphenyl boronic acid (0.447 g, 2.94 mmol), [1,1′-bis(diphenylphosphino)-ferrocene] complex with dichloromethane (1:1) (0.226 g, 0.196 mmol) and potassium phosphate (2.07 g, 9.8 mmol). The reaction mixture was heated to reflux temperature for 12 hours. The solvent was then evaporated to dryness and the residue was dissolved in 20 mL of ethyl acetate. The heterogeneous solution was washed 3 times with 10 mL of water and once with 10 mL of brine. The organic layer was dried over Na2SO4 and evaporated to dryness. The resulting brown solid was adsorbed on silica gel and purified by column chromatography (85:15 hexanes/ethyl acetate) to provide the title compound (0.539 g, 82.5% yield): ES-MS (m/z) 334 [M+1]+.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux temperature for 12 hours
  3. customThe solvent was then evaporated to dryness
  4. dissolutionthe residue was dissolved in 20 mL of ethyl acetate
  5. washThe heterogeneous solution was washed 3 times with 10 mL of water
  6. dry with materialThe organic layer was dried over Na2SO4
  7. customevaporated to dryness
  8. custompurified by column chromatography (85:15 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-7b0c5d8db50b43e4810ced0773785e43
Source dataset
uspto-grants-2007_05
Patent number
US07211594B2

Reaction notes

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