Dichloromethane → 5-[3-Chloro-5-(1-hydroxyethyl)-6-methoxy-2-methylphenyl]pyridine-2-carbonitrile

HRID 1499707Notes

Reaction equation

HRID 1499707 reaction equation
Br[C:2]1[C:3]([O:13][CH3:14])=[C:4]([CH:10]([OH:12])[CH3:11])[CH:5]=[C:6]([Cl:9])[C:7]=1[CH3:8].CC1(C)C(C)(C)OB([C:23]2[CH:24]=[CH:25][C:26]([C:29]#[N:30])=[N:27][CH:28]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].ClCCl>C(#N)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[Cl:9][C:6]1[C:7]([CH3:8])=[C:2]([C:23]2[CH:24]=[CH:25][C:26]([C:29]#[N:30])=[N:27][CH:28]=2)[C:3]([O:13][CH3:14])=[C:4]([CH:10]([OH:12])[CH3:11])[CH:5]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 164141882-Cyanopyridine-5-boronic acid pinacol esterHCID 866668161-(3-Bromo-5-chloro-2-methoxy-4-methylphenyl)ethanol

Product 1

HCID 866776485-[3-Chloro-5-(1-hydroxyethyl)-6-methoxy-2-methylphenyl]pyridine-2-carbonitrileYield 70%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 1-(3-bromo-5-chloro-2-methoxy-4-methylphenyl)ethanol (0.15 g, 0.54 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carbonitrile (from Frontier, 0.14 g, 0.59 mmol), sodium carbonate (110 mg, 1.1 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (52 mg, 0.064 mmol) in acetonitrile (4 mL)/water (1 mL) was degassed and then refilled with N2. The reaction was stirred at 95° C. for 2 h, cooled, diluted with ethyl acetate, washed with sat. NaHCO3, water, brine, and then dried over Na2SO4, filtered and concentrated. The crude product was purified by silica gel chromatography, eluting with 0 to 40% EtOAc in hexanes, to give the desired product (114 mg, 70%). LCMS calculated for C16H16ClN2O2 (M+H)+: m/z=303.1; Found: 303.0

Workup

  1. customwas degassed
  2. additionrefilled with N2
  3. temperaturecooled
  4. additiondiluted with ethyl acetate
  5. washwashed with sat. NaHCO3, water, brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with 0 to 40% EtOAc in hexanes

Sources & evidence

ORD record
ord-e93d8c2f3c264fea831cb8f7f6af07bf
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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