Sodium Hydroxide → 3-Amino-6-fluoro-2-(2'-fluoro[1,1'-biphenyl]-4-yl)-4-quinolinecarboxylic acid

HRID 1073263Notes

Reaction equation

HRID 1073263 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=O.[OH-:13].[Na+].Cl.[NH2:16][CH2:17][C:18]([C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[F:32])=[CH:22][CH:21]=1)=O>O.C(O)C.O.O1CCCC1>[NH2:16][C:17]1[C:18]([C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[F:32])=[CH:22][CH:21]=2)=[N:7][C:8]2[C:4]([C:5]=1[C:6]([OH:11])=[O:13])=[CH:3][C:2]([F:1])=[CH:10][CH:9]=2

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 2365665-FluoroisatinHCID 221583512-Amino-1-(2'-fluoro[1,1'-biphenyl]-4-yl)-ethanone hydrochloride

Product 1

HCID 150859603-Amino-6-fluoro-2-(2'-fluoro[1,1'-biphenyl]-4-yl)-4-quinolinecarboxylic acidYield 79.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 19096565Water ethanolSolvent

Procedure

To a stirred suspension of 4.13 g of 5-fluoroisatin in 40 ml of water was added a solution of 5.62 g of sodium hydroxide in 20 ml of water. This mixture was heated to 85°-90° C. and a warm solution of 9.3 g of 2-amino-1 (2'-fluoro[1,1'-biphenyl]-4-yl)ethanone, hydrochloride in 140 ml of ethanol:water (1:1) and 30 ml of tetrahydrofuran was added dropwise over 2 hours. This mixture was stirred at reflux for 2 hours, then the ethanol was distilled off. The reaction was filtered and the filtrate acidified to pH 4-5 with acetic acid. The resulting solid was collected, washed with water and crystallized from 400 ml of hot ethanol, giving 7.45 g of the desired product as a yellow solid, mp 248°-250° C.

Workup

  1. temperatureThis mixture was heated to 85°-90° C.
  2. temperatureat reflux for 2 hours
  3. distillationthe ethanol was distilled off
  4. filtrationThe reaction was filtered
  5. customThe resulting solid was collected
  6. washwashed with water
  7. customcrystallized from 400 ml of hot ethanol

Sources & evidence

ORD record
ord-95395aac5bb04592a69a49f71bcafa53
Source dataset
uspto-grants-1990_11
Patent number
US04968702

Reaction notes

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