Methanol → 6-(3-Acetylamino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinic acid

HRID 246936Notes

Reaction equation

HRID 246936 reaction equation
CO.[C:3]([NH:6][CH:7]1[CH2:11][CH2:10][N:9]([C:12]2[C:21]([F:22])=[CH:20][C:15]([C:16]([O:18]C)=[O:17])=[C:14]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=3[F:31])[N:13]=2)[CH2:8]1)(=[O:5])[CH3:4].[OH-].[Na+]>O1CCCC1.O.C(OCC)(=O)C>[C:3]([NH:6][CH:7]1[CH2:11][CH2:10][N:9]([C:12]2[C:21]([F:22])=[CH:20][C:15]([C:16]([OH:18])=[O:17])=[C:14]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=3[F:31])[N:13]=2)[CH2:8]1)(=[O:5])[CH3:4]

Participants

7

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 13821764Methyl 6-(3-acetylamino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinate

Product 1

HCID 138217726-(3-Acetylamino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinic acidYield 93%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a mixture of 30 ml of tetrahydrofuran, 10 ml of methanol and 4 ml of water was suspended 980 mg of methyl 6-(3-acetylamino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinate, and 5.3 ml of 1N aqueous sodium hydroxide solution was added thereto, after which the resulting mixture was subjected to reaction at 65° C. for 3 hours. Subsequently, the reaction mixture was added to a mixture of 50 ml of ethyl acetate and 50 ml of water, and the aqueous layer was separated, after which the pH thereof was adjusted to 2.0 with 1N hydrochloric acid. The crystals thus deposited were collected by filtration and washed successively with 2 ml of water and 2 ml of ethanol to obtain 880 mg (yield 93.0%) of 6-(3-acetylamino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinic acid having a melting point of 232°-234° C.

Workup

  1. additionwas added
  2. customafter which the resulting mixture was subjected to reaction at 65° C. for 3 hours
  3. customthe aqueous layer was separated
  4. filtrationThe crystals thus deposited were collected by filtration
  5. washwashed successively with 2 ml of water and 2 ml of ethanol

Sources & evidence

ORD record
ord-a663fd893c214f0291045bc02e6719fc
Source dataset
uspto-grants-1987_11
Patent number
US04704459

Reaction notes

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