Potassium Phosphate, Tribasic → 4-(benzyloxy)-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridin-2(1H)-one

HRID 1044402Notes

Reaction equation

HRID 1044402 reaction equation
[O-]P([O-])([O-])=O.[K+].[K+].[K+].CNC1CCCCC1NC.Br[C:20]1[CH:31]=[CH:30][C:23]([O:24][CH2:25][C:26]([CH3:29])([OH:28])[CH3:27])=[C:22]([O:32][CH3:33])[CH:21]=1.[CH2:34]([O:41][C:42]1[CH:47]=[CH:46][NH:45][C:44](=[O:48])[CH:43]=1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>O1CCOCC1.[Cu]I>[CH2:34]([O:41][C:42]1[CH:47]=[CH:46][N:45]([C:20]2[CH:31]=[CH:30][C:23]([O:24][CH2:25][C:26]([OH:28])([CH3:29])[CH3:27])=[C:22]([O:32][CH3:33])[CH:21]=2)[C:44](=[O:48])[CH:43]=1)[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 5510741-N,2-N-dimethylcyclohexane-1,2-diamineHCID 36077244-Benzyloxy-2(1H)-pyridoneHCID 595950491-(4-Bromo-2-methoxyphenoxy)-2-methylpropan-2-ol

Product 1

HCID 585802644-(benzyloxy)-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridin-2(1H)-oneYield 76.1%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of potassium phosphate tribasic (633 mg, 2.98 mmol), N1,N2-dimethylcyclohexane-1,2-diamine (141 mg, 0.99 mmol), copper(i) iodide (189 mg, 0.99 mmol), 1-(4-bromo-2-methoxyphenoxy)-2-methylpropan-2-ol (328 mg, 1.19 mmol) Part A and commercially available 4-(benzyloxy)pyridin-2(1H)-one (200 mg, 0.99 mmol) in dioxane (1.0 mL) was stirred in a sealed tube at 110° C. for 60 min. After removal of the solids by filtration and concentration of the filtrate, the crude product was subjected to flash chromatography (silica gel/CH2Cl2-10% MeOH/CH2Cl2 100:0 to 0:100 gradient employing LC-MS to identify fractions containing the desired product). The semi-pure product thus obtained was further purified by prep-HPLC (C18 column/Water:MeOH:TFA 90:10:0.1 to 10:90:0.1 gradient) to obtain 4-(benzyloxy)-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridin-2(1H)-one D-1 (298 mg, 74.3% yield) as a white foam. LC/MS 396 (M+H)+, tR 0.87 min (method 5); 1H NMR (400 MHz, Chloroform-D) δ ppm 7.34-7.47 (5H, m), 718 (1H, d, J=7.78 Hz), 6.96 (1H, d, J=8.53 Hz), 6.80-6.90 (2H, m), 6.28 (1H, d, J=2.51 Hz), 6.16 (1H, dd, J=7.65, 2.64 Hz), 5.08 (2H, s), 3.85 (5H, s), 1.35 (6H, s).

Workup

  1. customAfter removal of the solids
  2. filtrationby filtration and concentration of the filtrate
  3. additioncontaining the desired product)
  4. customThe semi-pure product thus obtained
  5. customwas further purified by prep-HPLC (C18 column/Water:MeOH:TFA 90:10:0.1 to 10:90:0.1 gradient)

Sources & evidence

ORD record
ord-0653a0d3e2ee4f198d0d17f6a654e706
Source dataset
uspto-grants-2013_10
Patent number
US08563583B2

Reaction notes

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