Dichloromethane → 4-[3-Chloro-5-(1-hydroxyethyl)-6-methoxy-2-methylphenyl]pyridine-2-carbonitrile

HRID 1499696Notes

Reaction equation

HRID 1499696 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:28]=[CH:27][N:26]=[C:25]([C:29]#[N:30])[CH:24]=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:28]=[CH:27][N:26]=[C:25]([C:29]#[N:30])[CH:24]=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 457862934-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carbonitrileHCID 866668161-(3-Bromo-5-chloro-2-methoxy-4-methylphenyl)ethanol

Product 1

HCID 866776404-[3-Chloro-5-(1-hydroxyethyl)-6-methoxy-2-methylphenyl]pyridine-2-carbonitrile

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 (0.30 g, 1.1 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carbonitrile (from Combi-Blocks, 0.27 g, 1.2 mmol), sodium carbonate (230 mg, 2.1 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (100 mg, 0.13 mmol) in acetonitrile (8 mL)/water (2 mL) was degassed and then refilled with N2. The reaction was stirred at 95° C. for 2 hours, then cooled and diluted with ethyl acetate, washed with sat. NaHCO3, water, brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by silica gel chromatography, eluting with 0 to 40% EtOAc in hexanes (0.249 g, 75%). 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 (0.249 g, 75%)

Sources & evidence

ORD record
ord-7a1ecbf00e174301b393037fbd97a0f8
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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