Potassium Carbonate → Methyl 1-{[(4'-chloro-4-methylbiphenyl-3-yl)acetyl]amino}-4-methoxy-4-(methoxymethyl)cyclohexanecarboxylate

HRID 922131Notes

Reaction equation

HRID 922131 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[C:10]([CH2:15][C:16]([OH:18])=O)[CH:9]=2)=[CH:4][CH:3]=1.S(Cl)(Cl)=O.C(=O)([O-])[O-].[K+].[K+].[NH2:29][C:30]1([C:41]([O:43][CH3:44])=[O:42])[CH2:35][CH2:34][C:33]([O:39][CH3:40])([CH2:36][O:37][CH3:38])[CH2:32][CH2:31]1>C(#N)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[C:10]([CH2:15][C:16]([NH:29][C:30]3([C:41]([O:43][CH3:44])=[O:42])[CH2:31][CH2:32][C:33]([O:39][CH3:40])([CH2:36][O:37][CH3:38])[CH2:34][CH2:35]3)=[O:18])[CH:9]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 66707678(4'-Chloro-4-methylbiphenyl-3-yl)acetic acidHCID 71246293Methyl 1-amino-4-methoxy-4-(methoxymethyl)cyclohexanecarboxylate

Product 1

HCID 90413777Methyl 1-{[(4'-chloro-4-methylbiphenyl-3-yl)acetyl]amino}-4-methoxy-4-(methoxymethyl)cyclohexanecarboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

574 mg (2.20 mmol) of (4′-chloro-4-methylbiphenyl-3-yl)acetic acid (EP 2029531 A1 and US 2009/298828 A1) were dissolved in 0.9 g (12.5 mmol) of thionyl chloride. The reaction mixture was stirred at 80° C. for 1 h and then concentrated. The residue was dissolved in 5 ml of acetonitrile. 816 mg (5.90 mmol) of potassium carbonate were added to 390 mg (1.69 mmol) of the compound from Example 24A in 10 ml of acetonitrile. With ice-cooling, the solution of the acid chloride was added dropwise, and the mixture was stirred at room temperature overnight. The mixture was then concentrated, the residue was taken up in ice-water and extracted repeatedly with dichloromethane, and the combined organic phases were washed repeatedly with 1N aqueous hydrogen chloride solution and saturated aqueous sodium bicarbonate solution, dried over sodium sulphate, filtered and concentrated. This gave 570 mg of the title compound as a diastereomer mixture which were reacted without further purification.

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in 5 ml of acetonitrile
  3. temperatureWith ice-cooling
  4. stirringthe mixture was stirred at room temperature overnight
  5. concentrationThe mixture was then concentrated
  6. extractionextracted repeatedly with dichloromethane
  7. washthe combined organic phases were washed repeatedly with 1N aqueous hydrogen chloride solution and saturated aqueous sodium bicarbonate solution
  8. dry with materialdried over sodium sulphate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThis gave 570 mg of the title compound as a diastereomer mixture which were reacted without further purification

Sources & evidence

ORD record
ord-95a08e5febb6429796245cf3f0706da8
Source dataset
uspto-grants-2016_03
Patent number
US09278925B2

Reaction notes

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