Hydrochloric Acid → 4-(4-Benzyloxycarbonylamino-3-fluorophenyl)pyridine-2-carboxylic acid

HRID 492739Notes

Reaction equation

HRID 492739 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][N:21]=[C:20]([C:24]([O:26]C)=[O:25])[CH:19]=2)=[CH:14][C:13]=1[F:28])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.O.[OH-].[Li+].Cl>C(O)C.CO.CN(C)C=O.CCCCCC.C(OCC)C>[CH2:1]([O:8][C:9]([NH:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][N:21]=[C:20]([C:24]([OH:26])=[O:25])[CH:19]=2)=[CH:14][C:13]=1[F:28])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 23153492Methyl 4-(4-benzyloxycarbonylamino-3-fluorophenyl)pyridine-2-carboxylate

Product 1

HCID 231533734-(4-Benzyloxycarbonylamino-3-fluorophenyl)pyridine-2-carboxylic acidYield 86.1%

Reagents, catalysts & solvents 5

HCID 702EthanolSolventHCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8058HexaneSolvent

Procedure

Methyl 4-(4-benzyloxycarbonylamino-3-fluorophenyl)pyridine-2-carboxylate (1.02 g) was dissolved in a mixed solvent of ethanol (25 ml), methanol (50 ml) and N,N-dimethylformamide (7.5 ml), and then water (7.5 ml) was added. Lithium hydroxide monohydrate (185 mg) was added thereto at room temperature while stirring, followed by stirring at room temperature for 1.5 hrs. To the reaction mixture was added 1 N HCl (30 ml), followed by concentrating under a reduced pressure. To the resultant residue was added a mixed solvent of ethyl acetate (100 ml) and tetrahydrofuran (100 ml) to partition. The organic layer was washed with brine (50 ml×3), and dried over anhydrous sodium sulfate. The solvent was evaporated to give a solid, which was then suspended in a mixed solvent of diethyl ether (20 ml) and hexane (20 ml), filtered, and dried under aeration to provide the titled compound (846 mg, 86.1%) as a pale brown solid.

Workup

  1. stirringby stirring at room temperature for 1.5 hrs
  2. concentrationby concentrating under a reduced pressure
  3. additionTo the resultant residue was added a mixed solvent of ethyl acetate (100 ml) and tetrahydrofuran (100 ml)
  4. customto partition
  5. washThe organic layer was washed with brine (50 ml×3)
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated
  8. customto give a solid, which
  9. filtrationfiltered
  10. customdried under aeration

Sources & evidence

ORD record
ord-39687eda882b47ec8d8fd89b425a8429
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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