4-{4-[5-(3-tert-Butyl-phenylcarbamoyl)-pyridin-2-yl]-piperazin-1-yl}-benzoic acid ethyl ester → 4-{4-[5-(3-tert-Butyl-phenylcarbamoyl)-pyridin-2-yl]-piperazin-1-yl}-benzoic acid

HRID 2190595Notes

Reaction equation

HRID 2190595 reaction equation
C([O:3][C:4](=[O:36])[C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23](=[O:35])[NH:24][C:25]4[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([CH3:34])([CH3:33])[CH3:32])[CH:26]=4)=[CH:19][N:18]=3)[CH2:13][CH2:12]2)=[CH:7][CH:6]=1)C>C1COCC1.O>[C:31]([C:27]1[CH:26]=[C:25]([NH:24][C:23]([C:20]2[CH:21]=[CH:22][C:17]([N:14]3[CH2:13][CH2:12][N:11]([C:8]4[CH:7]=[CH:6][C:5]([C:4]([OH:36])=[O:3])=[CH:10][CH:9]=4)[CH2:16][CH2:15]3)=[N:18][CH:19]=2)=[O:35])[CH:30]=[CH:29][CH:28]=1)([CH3:34])([CH3:32])[CH3:33]

Participants

4

Reactant 1

HCID 593180734-{4-[5-(3-tert-Butyl-phenylcarbamoyl)-pyridin-2-yl]-piperazin-1-yl}-benzoic acid ethyl ester

Product 1

HCID 462019764-{4-[5-(3-tert-Butyl-phenylcarbamoyl)-pyridin-2-yl]-piperazin-1-yl}-benzoic acidYield 13%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-{4-[5-(3-tert-Butyl-phenylcarbamoyl)-pyridin-2-yl]-piperazin-1-yl}-benzoic acid ethyl ester (50 mg, 0.11 mmol) in THF (10 mL) and water (2 mL) was treated with LiOH monohydrate (8.6 mg, 0.22 mmol). After stirring at rt for 4 h the mixture was treated with another portion of LiOH monohydrate (9 mg, 0.22 mmol) and the mixture was stirred at 50° C. for 16 h. The mixture was then cooled and partitioned between EtOAc and water. The acidity of the water layer was adjusted to pH 5 with 1N aqueous HCl. The water layer was extracted twice more with EtOAc and the combined EtOAc layer was dried, filtered and concentrated. The residue was chromatographed on a silica gel column with 0-3% MeOH in CH2Cl2 gradient to afford the product (6 mg; Yield: 13%). HRMS m/z calcd for C27H30N4O3 [M+H]+: 459.2391. Found: 459.2388.

Workup

  1. stirringthe mixture was stirred at 50° C. for 16 h
  2. temperatureThe mixture was then cooled
  3. custompartitioned between EtOAc and water
  4. extractionThe water layer was extracted twice more with EtOAc
  5. dry with materialthe combined EtOAc layer was dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was chromatographed on a silica gel column with 0-3% MeOH in CH2Cl2 gradient
  9. customto afford the product (6 mg; Yield: 13%)

Sources & evidence

ORD record
ord-79046310a17247cbbeac8bac0b09b871
Source dataset
uspto-grants-2012_12
Patent number
US08324385B2

Reaction notes

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