Sodium Bicarbonate → 3-Chloro-4-(5-fluoro-6-hydroxyquinolin-2-yl)benzoic acid

HRID 1627675Notes

Reaction equation

HRID 1627675 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([OH:13])[C:8]=2[F:12])[N:3]=1.B([C:17]1[CH:25]=[CH:24][C:20]([C:21]([OH:23])=[O:22])=[CH:19][C:18]=1[Cl:26])(O)O.C([O-])(O)=O.[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:26][C:18]1[CH:19]=[C:20]([CH:24]=[CH:25][C:17]=1[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([OH:13])[C:8]=2[F:12])[N:3]=1)[C:21]([OH:23])=[O:22]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 17750227SimtuzumabHCID 866980752-Chloro-5-fluoroquinolin-6-ol2×

Product 1

HCID 574048783-Chloro-4-(5-fluoro-6-hydroxyquinolin-2-yl)benzoic acidYield 15.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
95 °C

Procedure

2-Chloro-5-fluoroquinolin-6-ol (Intermediate 16, 1.0 mmol) and 4-borono-3-chlorobenzoic acid (1.1 mmol) were mixed with 5% (Ph3P)4Pd and 4.0 mmol of NaHCO3 in 20 ml 50% dioxane/water. The mixture was degassed three times by evacuation and argon filling and heated at 95° C. overnight. The reaction was diluted with 20 ml of water and filtered. The filtrate was acidified with 1N HCl to pH=4. The precipitate was filtered and washed with water, dried. The crude was purified by column using AcOH/MeOH/EtOAC (1/5/94) as solvent B and hexanes as solvent A with gradient 2 to 100%. The fractions with compound were pooled and evaporated to obtain white solid. The solid was triturated with diisopropyl ether. 50 mg of final product was obtained. 1H-NMR (DMSO-d6, 300 MHz, TMS): δ 10.55 (b, 1H), 8.47 (d, 1H), 8.01-8.03 (m, 2H), 7.79 (m, 3H), 7.56 (t, 1H). MS (ESI): m/z=316.3 [M−H]−.

Workup

  1. customThe mixture was degassed three times by evacuation and argon filling
  2. additionThe reaction was diluted with 20 ml of water
  3. filtrationfiltered
  4. filtrationThe precipitate was filtered
  5. washwashed with water
  6. customdried
  7. customThe crude was purified by column
  8. customevaporated
  9. customto obtain white solid
  10. customThe solid was triturated with diisopropyl ether

Sources & evidence

ORD record
ord-b0d9ff57a196495889b89d1915f8385d
Source dataset
uspto-grants-2014_07
Patent number
US08785643B2

Reaction notes

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