Sodium Hydroxide → 6-[2-(3-Chloro-phenyl)-3-cyclopentyl-propionylamino]nicotinic acid

HRID 966786Notes

Reaction equation

HRID 966786 reaction equation
C[O:2][C:3](=[O:27])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:26])[CH:12]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=2)[CH2:13][CH:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)=[N:6][CH:5]=1.[OH-].[Na+]>O1CCCC1.O.CO>[Cl:25][C:21]1[CH:20]=[C:19]([CH:12]([CH2:13][CH:14]2[CH2:15][CH2:16][CH2:17][CH2:18]2)[C:11]([NH:10][C:7]2[CH:8]=[CH:9][C:4]([C:3]([OH:27])=[O:2])=[CH:5][N:6]=2)=[O:26])[CH:24]=[CH:23][CH:22]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 545579716-[2-(3-Chloro-phenyl)-3-cyclopentyl-propionylamino]-nicotinic acid methyl ester

Product 1

HCID 223151506-[2-(3-Chloro-phenyl)-3-cyclopentyl-propionylamino]nicotinic acidYield 44.9%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 6-[2-(3-chloro-phenyl)-3-cyclopentyl-propionylamino]-nicotinic acid methyl ester (146.9 mg, 0.38 mmol) in tetrahydrofuran/water/methanol (10 mL, 3:1:1) at 25° C. was treated with a 2N aqueous sodium hydroxide solution (0.4 mL, 0.80 mmol). The reaction mixture was stirred at 25° C. for 4 d. At this time, the reaction was concentrated in vacuo. The residue was diluted with water (50 mL) and extracted with diethyl ether (1×50 mL). The aqueous layer was acidified to pH=1 by the dropwise addition of a 3N aqueous hydrochloric acid solution. This solution was extracted with a solution of methylene chloride/methanol (3:1, 3×75 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting solid was triturated with diethyl ether/hexanes (2:1) to afford 6-[2-(3-chloro-phenyl)-3-cyclopentyl-propionylamino]-nicotinic acid (63.6 mg, 44.4%) as a white solid: mp 251-255° C.; EI-HRMS m/e calcd for C20H21ClN2O3 (M+) 372.1240, found 372.1250.

Workup

  1. concentrationAt this time, the reaction was concentrated in vacuo
  2. additionThe residue was diluted with water (50 mL)
  3. extractionextracted with diethyl ether (1×50 mL)
  4. additionThe aqueous layer was acidified to pH=1 by the dropwise addition of a 3N aqueous hydrochloric acid solution
  5. extractionThis solution was extracted with a solution of methylene chloride/methanol (3:1, 3×75 mL)
  6. dry with materialThe combined organic layers were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe resulting solid was triturated with diethyl ether/hexanes (2:1)

Sources & evidence

ORD record
ord-ba7d55c12c2b4d258556d7c1b3e2cfd1
Source dataset
uspto-grants-2005_10
Patent number
US06951945B2

Reaction notes

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