Phenol → 4-(2-Phenoxyquinolin-6-ylmethyl)-3-oxopiperazine-1-carboxylic acid benzyl ester

HRID 1432917Notes

Reaction equation

HRID 1432917 reaction equation
[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:8]([O:15][C:16]([N:18]1[CH2:23][CH2:22][N:21]([CH2:24][C:25]2[CH:26]=[C:27]3[C:32](=[CH:33][CH:34]=2)[N:31]=[C:30](Cl)[CH:29]=[CH:28]3)[C:20](=[O:36])[CH2:19]1)=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[OH-].[K+].[OH-].[Na+]>C(Cl)Cl>[CH2:8]([O:15][C:16]([N:18]1[CH2:23][CH2:22][N:21]([CH2:24][C:25]2[CH:26]=[C:27]3[C:32](=[CH:33][CH:34]=2)[N:31]=[C:30]([O:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:29]=[CH:28]3)[C:20](=[O:36])[CH2:19]1)=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

6

Reactant 4

HCID 996PhenolHCID 14797Potassium HydroxideHCID 14798Sodium HydroxideHCID 54453418HCID 54453418, compound

Product 1

HCID 544928964-(2-Phenoxyquinolin-6-ylmethyl)-3-oxopiperazine-1-carboxylic acid benzyl esterYield 91.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of phenol (15.1 g, 160 mmol) and 4-(2-chloroquinolin-6-ylmethyl)-3-oxopiperazine-1-carboxylic acid benzyl ester (6.60 g, 16.1 mmol) is melted together at 70° C. until a homogeneous mixture is obtained. Potassium hydroxide (3.15 g, 56.1 mmol) is added and the resulting mixture is heated overnight at 120° C. After 24 hours, the brown/black residue is cooled to room temperature, diluted with CH2Cl2 and stirred with 1N NaOH (100 mL) for 30 minutes. The two layers are separated and the aqueous layer is extracted with CH2Cl2. The combined organic layers are washed with 1N NaOH, saturated NaCl, dried over Na2SO4, filtered and concentrated. The crude title compound (6.92 g, 14.8 mmol) is obtained as a beige foam and used in the subsequent step without further purification. 1H NMR (CDCl3, 300 MHz) δ8.07 (d, 1H), 7.76 (d, 1H), 7.63 (s, 1H), 7.50 (dd, 1H), 7.42 (m, 2H), 7.34 (m, 6H), 7.25 (m, 2), 7.09 (d, 1H), 5.14 (s, 2), 4.75 (s, 2H), 4.27 (s, 2H), 3.66 (m, 2H), 3.30 (bs, 2H).

Workup

  1. customis melted together at 70° C. until a homogeneous mixture
  2. customis obtained
  3. temperaturethe brown/black residue is cooled to room temperature
  4. customThe two layers are separated
  5. extractionthe aqueous layer is extracted with CH2Cl2
  6. washThe combined organic layers are washed with 1N NaOH, saturated NaCl
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-ad5fd5fe5de34d6e89ef8af991e374c3
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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