2-Methylphenyl boronic acid → HCID 86665677, compound

HRID 81014Notes

Reaction equation

HRID 81014 reaction equation
[Cl:1][C:2]1[N:9]=[C:8]([CH:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)[CH:7]=[C:6]([C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=2)[C:3]=1[C:4]#[N:5].[C:22]1([CH3:31])[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1B(O)O>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Cl:1][C:2]1[N:9]=[C:8]([CH:10]2[CH2:11][CH2:12][CH2:13][CH2:14]2)[CH:7]=[C:6]([C:15]2[CH:16]=[CH:17][C:18]([O:21][C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[CH3:31])=[CH:19][CH:20]=2)[C:3]=1[C:4]#[N:5]

Participants

5

Reactant 2

HCID 27332672-Methylphenyl boronic acidHCID 1363723472-Chloro-6-cyclopentyl-4-(4-hydroxyphenyl)nicotinonitrile2×

Product 1

HCID 86665677HCID 86665677, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-chloro-6-cyclopentyl-4-(4-hydroxyphenyl)nicotinonitrile (20 mg, 0.067 mmol, product A from Step 4 of Example 2), o-tolylboronic acid (36.4 mg, 0.268 mmol), copper(II) acetate (14.59 mg, 0.080 mmol) and 4 A molecular sieves (100 mg) in dichloromethane (3 mL) was stirred at room temperature while opening to the air for 40 h. The mixture was filtered through a CELITE® pad and the pad rinsed with ethyl acetate (50 mL). The filtrate was washed with saturated sodium bicarbonate (5 mL), water (5 mL), brine (5 mL), dried (MgSO4) and concentrated. Silica gel chromatography, eluting with 0-15% ethyl acetate in hexanes, gave 2-chloro-6-cyclopentyl-4-(4-(o-tolyloxy)phenyl)nicotinonitrile as a colorless liquid (15 mg, 58% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.50 (2H, δ, J=8.53 Hz), 7.07-7.32 (5H, m), 6.91-7.03 (2H, m), 3.05-3.28 (1H, m), 2.20 (3H, s), 1.98-2.13 (2H, m), 1.60-1.91 (6H, m); MS (ES+) m/z: 389 (M+H); LC retention time: 4.578 min (analytical HPLC Method A).

Workup

  1. filtrationThe mixture was filtered through a CELITE® pad
  2. washthe pad rinsed with ethyl acetate (50 mL)
  3. washThe filtrate was washed with saturated sodium bicarbonate (5 mL), water (5 mL), brine (5 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. washSilica gel chromatography, eluting with 0-15% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-21b0a40c892b4bd68d56e7b53cf0c117
Source dataset
uspto-grants-2014_09
Patent number
US08846673B2

Reaction notes

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