Sodium Hydroxide → 6-(2-Biphenyl-4-yl-3-cyclopentyl-propionylamino)-nicotinic acid

HRID 1935243Notes

Reaction equation

HRID 1935243 reaction equation
C[O:2][C:3](=[O:32])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:31])[CH:12]([C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[CH:21][CH:20]=2)[CH2:13][CH:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)=[N:6][CH:5]=1.[OH-].[Na+]>CO>[C:22]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:21]=[CH:20][C:19]([CH:12]([CH2:13][CH:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)[C:11]([NH:10][C:7]2[CH:8]=[CH:9][C:4]([C:3]([OH:32])=[O:2])=[CH:5][N:6]=2)=[O:31])=[CH:24][CH:23]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 101134046-(2-Biphenyl-4-yl-3-cyclopentyl-propionylamino)-nicotinic acid methyl ester

Product 1

HCID 101124776-(2-Biphenyl-4-yl-3-cyclopentyl-propionylamino)-nicotinic acidYield 28.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 6-(2-biphenyl-4-yl-3-cyclopentyl-propionylamino)-nicotinic acid methyl ester (prepared in Example 22, 100 mg, 0.23 mmol) in methanol (2 mL) was treated with a 1N aqueous sodium hydroxide solution (350 mL, 0.35 mmol). The reaction mixture was heated under reflux for 30 min and then allowed to cool to 25° C. The reaction mixture was then concentrated in vacuo. The resulting residue was partitioned between water and ethyl acetate, and the layers were separated. The aqueous layer was further extracted with ethyl acetate (1×25 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 1/1 hexanes/ethyl acetate then 100% methanol) afforded 6-(2-biphenyl-4-yl-3-cyclopentyl-propionylamino)-nicotinic acid (27 mg, 28%) as a white solid: mp 271-272° C. (dec); FAB-HRMS m/e calcd for C26H26N2O3 (M+H)+ 415.2021, found 415.2010.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureunder reflux for 30 min
  3. concentrationThe reaction mixture was then concentrated in vacuo
  4. customThe resulting residue was partitioned between water and ethyl acetate
  5. customthe layers were separated
  6. extractionThe aqueous layer was further extracted with ethyl acetate (1×25 mL)
  7. dry with materialThe combined organic extracts were dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b790182d91b949bdbcd4b0d851dfbc90
Source dataset
uspto-grants-2002_05
Patent number
US06384220B2

Reaction notes

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