Pyridine → 4-chloro-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridin-2(1H)-one

HRID 1044408

Reaction equation

HRID 1044408 reaction equation
N1C=CC=CC=1.[Cl:7][C:8]1[CH:13]=[CH:12][NH:11][C:10](=[O:14])[CH:9]=1.[OH:15][C:16]([CH3:31])([CH3:30])[CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][C:20]=1[O:28][CH3:29]>C(Cl)Cl.CO>[Cl:7][C:8]1[CH:13]=[CH:12][N:11]([C:22]2[CH:23]=[CH:24][C:19]([O:18][CH2:17][C:16]([OH:15])([CH3:31])[CH3:30])=[C:20]([O:28][CH3:29])[CH:21]=2)[C:10](=[O:14])[CH:9]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 27576114-Chloropyridin-2-olHCID 585798634-(2-Hydroxy-2-methylpropoxy)-3-methoxyphenylboronic acid

Product 1

HCID 585802944-chloro-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridin-2(1H)-oneYield 62.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

Pyridine (1.2 mL, 15.4 mmol) was added to a stirred solution of commercially available 4-chloropyridin-2(1H)-one (100 mg, 0.77 mmol), 4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenylboronic acid Part C (278 mg, 1.16 mmol), and copper (II) acetate, monohydrate (154 mg, 0.77 mmol) in CH2Cl2 (7 mL) and MeOH (0.7 mL). The reaction mixture stirred at RT under the presence of air overnight (21 hours). The reaction mixture was diluted with CH2Cl2, washed with IN HCl, sat. NaHCO3, dried (Na2SO4), and concentrated. The crude product was purified using preparative HPLC (C18 column/10:90:0.1 to 90:10:0.1 MeOH—H2O-TFA) to afford the desired product 4-chloro-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridin-2(1H)-one 9D (169 mg, 0.49 mmol, 62.8% yield) as a brown gum. LC/MS 324 (M+H)+, tR 0.75 min (method 5)

Workup

  1. washwashed with IN HCl, sat. NaHCO3
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customThe crude product was purified

Sources & evidence

ORD record
ord-febe04c268f74042b1c1e8a49da96f38
Source dataset
uspto-grants-2013_10
Patent number
US08563583B2

Linked notes

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