Dimethylformamide → 6,8-Difluoro-1-(2-fluoroethyl)-1,4-dihydro-7-(4-hydroxypiperazin-1-yl)-4-oxoquinoline-3-carboxylic acid

HRID 1788980Notes

Reaction equation

HRID 1788980 reaction equation
Cl.Cl.[OH:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.C(N(CC)CC)C.CN(C)C=O.[F:22][C:23]1[CH:24]=[C:25]2[C:30](=[C:31]([F:34])[C:32]=1F)[N:29]([CH2:35][CH2:36][F:37])[CH:28]=[C:27]([C:38]([OH:40])=[O:39])[C:26]2=[O:41]>C(O)(=O)C>[F:22][C:23]1[CH:24]=[C:25]2[C:30](=[C:31]([F:34])[C:32]=1[N:7]1[CH2:8][CH2:9][N:4]([OH:3])[CH2:5][CH2:6]1)[N:29]([CH2:35][CH2:36][F:37])[CH:28]=[C:27]([C:38]([OH:40])=[O:39])[C:26]2=[O:41]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 12463394Piperazin-1-ol dihydrochlorideHCID 127709081-(2-Fluoroethyl)-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

Product 1

HCID 30658506,8-Difluoro-1-(2-fluoroethyl)-1,4-dihydro-7-(4-hydroxypiperazin-1-yl)-4-oxoquinoline-3-carboxylic acidYield 169.4%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

1-Hydroxypiperazine dihydrochloride (1.03 g), triethylamine (35.6 g) and dimethylformamide (85 ml) are added to 6,7,8-trifluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (8.5 g), which is prepared by the procedure described in Japanese Patent First Publication No. 30964/1981, and the mixture is stirred for 1.5 hours at 100°-105° C. After cooling to room temperature, the reaction mixture is poured into ice-water (500 ml) and the pH is adjusted to 7.0 with 50% aqueous acetic acid. The resulting precipitate is filtered, washed with water and then recrystallized from dimethylformamide. Ethanol (100 ml) is added to the resulting pale yellow needles and the mixture is refluxed for 1.5 hours. After cooling the mixture to room temperature, the insoluble substance is filtered to yield 6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-7-(4-hydroxypiperazin-1-yl)-4-oxoquinoline-3-carboxylic acid (3.7 g) as pale yellow needles, m.p. 220°-229° C. (decomposition).

Workup

  1. customis prepared by the procedure
  2. filtrationThe resulting precipitate is filtered
  3. washwashed with water
  4. customrecrystallized from dimethylformamide
  5. additionEthanol (100 ml) is added to the resulting pale yellow needles
  6. temperaturethe mixture is refluxed for 1.5 hours
  7. temperatureAfter cooling the mixture to room temperature
  8. filtrationthe insoluble substance is filtered

Sources & evidence

ORD record
ord-62d5549876a64c209d2645a79fd100cc
Source dataset
uspto-grants-1987_08
Patent number
US04686221

Reaction notes

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