Hydrochloric Acid → (RS)-7-fluoro-1-methyl-4-oxo-8-(3-phenyl-1-piperazinyl)-1,4-dihydrobenzo[b][1,8]naphthyridine-3-carboxylic acid

HRID 344870Notes

Reaction equation

HRID 344870 reaction equation
C([O:3][C:4]([C:6]1[C:7](=[O:34])[C:8]2[CH:9]=[C:10]3[CH:20]=[C:19]([F:21])[C:18]([N:22]4[CH2:27][CH2:26][NH:25][CH:24]([C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=5)[CH2:23]4)=[CH:17][C:11]3=[N:12][C:13]=2[N:14]([CH3:16])[CH:15]=1)=[O:5])C.Cl.[OH-].[K+]>C(O)(=O)C.O>[F:21][C:19]1[C:18]([N:22]2[CH2:27][CH2:26][NH:25][CH:24]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:23]2)=[CH:17][C:11]2=[N:12][C:13]3[N:14]([CH3:16])[CH:15]=[C:6]([C:4]([OH:5])=[O:3])[C:7](=[O:34])[C:8]=3[CH:9]=[C:10]2[CH:20]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 53735832(RS)-3-ethoxycarbonyl-7-fluoro-1-methyl-4-oxo-8-(3-phenyl-1-piperazinyl)-1,4-dihydrobenzo[b][1,8]naphthyridine

Product 1

HCID 9889025(RS)-7-fluoro-1-methyl-4-oxo-8-(3-phenyl-1-piperazinyl)-1,4-dihydrobenzo[b][1,8]naphthyridine-3-carboxylic acidYield 69.7%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

A solution of (RS)-3-ethoxycarbonyl-7-fluoro-1-methyl-4-oxo-8-(3-phenyl-1-piperazinyl)-1,4 -dihydrobenzo[b][1,8]naphthyridine (1.07 g) in acetic acid (10 cc) and 17.5% strength aqueous hydrochloric acid solution (10 cc) is heated to a temperature in the region of 100° C. for 40 minutes. The reaction mixture is concentrated to dryness under reduced pressure (20 kPa) at approximately 60° C. The dry extract is taken up with ethanol (10 cc), drained and washed with ethanol (2×10 cc) and ethyl ether (2×10 cc). The solid obtained is suspended in water (30 cc) and heated to a temperature in the region of 95° C. After the addition of 2 N aqueous potassium hydroxide (1.35 cc) and stirring for 30 minutes, the solid is drained at approximately 95° C. and washed with water (3×20 cc) at approximately 80° C., ethanol (3×15 cc) at approximately 60° C. and ethyl ether (3×20 cc). After 1 recrystallization in a mixture of dimethylformamide (12 cc) and ethanol (6 cc), (RS)-7-fluoro-1-methyl-4-oxo-8-(3-phenyl-1-piperazinyl)-1,4-dihydrobenzo[b][1,8]naphthyridine-3-carboxylic acid (0.7 g) is obtained in the form of a yellow solid, m.p. 265° C.

Workup

  1. concentrationThe reaction mixture is concentrated to dryness under reduced pressure (20 kPa) at approximately 60° C
  2. extractionThe dry extract
  3. washwashed with ethanol (2×10 cc) and ethyl ether (2×10 cc)
  4. customThe solid obtained
  5. customis drained at approximately 95° C.
  6. washwashed with water (3×20 cc) at approximately 80° C.
  7. customat approximately 60° C.
  8. customAfter 1 recrystallization
  9. additionin a mixture of dimethylformamide (12 cc) and ethanol (6 cc)

Sources & evidence

ORD record
ord-a819f11413b04f16b51052cd5bce39a9
Source dataset
uspto-grants-1991_10
Patent number
US05053509

Reaction notes

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