Dichloromethane → 1-(3-Fluoro-5-(6-methoxynaphthalen-2-yl)pyridin-4-yl)ethanol

HRID 1897576Notes

Reaction equation

HRID 1897576 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8](B(O)O)[CH:7]=[CH:6]2.Br[C:17]1[CH:18]=[N:19][CH:20]=[C:21]([F:26])[C:22]=1[CH:23]([OH:25])[CH3:24].C(=O)([O-])[O-].[Na+].[Na+].C(Cl)Cl>CN(C=O)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]>[F:26][C:21]1[CH:20]=[N:19][CH:18]=[C:17]([C:8]2[CH:7]=[CH:6][C:5]3[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=3)[CH:9]=2)[C:22]=1[CH:23]([OH:25])[CH3:24]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 46416926-Methoxy-2-naphthaleneboronic acidHCID 699379091-(3-Bromo-5-Fluoro-pyridin-4-yl)-ethanol

Product 1

HCID 699373971-(3-Fluoro-5-(6-methoxynaphthalen-2-yl)pyridin-4-yl)ethanolYield 51%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 6-methoxynaphthalen-2-ylboronic acid (333 mg, 1.650 mmol), 1-(3-bromo-5-fluoropyridin-4-yl)ethanol 4a (330 mg, 1.5 mmol), sodium carbonate (2M in water, 1.5 mL, 3.00 mmol), PdCl2(dppf).CH2Cl2 adduct (61.2 mg, 0.075 mmol) in DMF (6 mL) was heated to 100° C. for 2 hrs. The mixture was quenched with sat NaHCO3 and extracted with EtOAc two times, dried over magnesium sulfate, filtered, concentrated. The residue was purified via Biotage (20-60% EtOAc/heptane; SNAP25 column) giving the title compound (227 mg, 51%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.62 (dd, J=6.7, 1.0 Hz, 3H), 3.96 (s, 3H), 4.99 (q, J=6.7 Hz, 1H), 7.19-7.26 (m, 2H), 7.36 (dd, J=8.4, 1.7 Hz, 1H), 7.70 (s, 1H), 7.78 (d, J=8.9 Hz, 1H), 7.83 (d, J=8.5 Hz, 1H), 8.40 (s, 1H), 8.48 (d, J=2.7 Hz, 1H). LC-MS (M+1) 298.0, t=1.49 min.

Workup

  1. customThe mixture was quenched with sat NaHCO3
  2. extractionextracted with EtOAc two times
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified via Biotage (20-60% EtOAc/heptane; SNAP25 column)

Sources & evidence

ORD record
ord-5527eace12414eaf8eef5e23bf530026
Source dataset
uspto-grants-2013_08
Patent number
US08519134B2

Reaction notes

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