Sodium Carbonate → 6-(4-(1-Hydroxyethyl)pyridin-3-yl)-2-naphthonitrile

HRID 1897573Notes

Reaction equation

HRID 1897573 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[CH:15]=[C:14]([C:19]#[N:20])[CH:13]=[CH:12]3)O1.Br[C:23]1[CH:24]=[N:25][CH:26]=[CH:27][C:28]=1[CH:29]([OH:31])[CH3:30].C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[OH:31][CH:29]([C:28]1[CH:27]=[CH:26][N:25]=[CH:24][C:23]=1[C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]=[C:14]([C:19]#[N:20])[CH:13]=[CH:12]2)[CH3:30]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 667878886-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-naphthonitrileHCID 667978531-(3-Bromopyridin-4-yl)ethanol

Product 1

HCID 699374566-(4-(1-Hydroxyethyl)pyridin-3-yl)-2-naphthonitrile

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-naphthonitrile 2c (233 mg, 0.835 mmol), 1-(3-bromopyridin-4-yl)ethanol (153 mg, 0.759 mmol, prepared according to the procedure described in Heterocyles 1993, 35, 151-169), sodium carbonate (2M in water, 0.759 mL, 1.518 mmol), bis(triphenylphosphine)palladium(II) chloride (26.6 mg, 0.038 mmol) in DMF (3.035 mL) was heated to 100° C. for 1 hr. The mixture was quenched with saturated NaHCO3 solution and extracted with EtOAc twice. The combined extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified twice via Biotage (20-100% EtOAc/heptane; 25M column). 47 mg of racemic title compound was isolated as white solid, and was subsequently separated by chiral HPLC (ChiralPak AS-H column, 2.1×250 mm, 16 mL/min, 70% heptane 30% ethanol) to 2-(enantiomer-1) (13 mg, 6%) (retention time: 11.74 min) and 2-(enantiomer-2) (12 mg, 6%) (retention time: 19.90 min). 1H NMR (400 MHz, CDCl3) δ ppm 1.34 (d, J=6.3 Hz, 3H), 5.28 (q, J=6.5 Hz, 1H), 7.59 (d, J=8.3 Hz, 1H), 7.75 (d, J=7.9 Hz, 1H), 7.91 (s, 1H), 8.39 (d, J=5.0 Hz, 1H), 8.55 (s, 1H), 8.70 (d, J=6.2 Hz, 1H). LC-MS (M+1) 275.1, t=1.06 min.

Workup

  1. customprepared
  2. customThe mixture was quenched with saturated NaHCO3 solution
  3. extractionextracted with EtOAc twice
  4. dry with materialThe combined extracts were dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified twice via Biotage (20-100% EtOAc/heptane; 25M column)

Sources & evidence

ORD record
ord-aa3c795d5c034034a7f895217fd4c8c6
Source dataset
uspto-grants-2013_08
Patent number
US08519134B2

Reaction notes

Loading…