Sodium Thiosulfate → 8-Bromoquinoline-4-carboxylic acid

HRID 2207719Notes

Reaction equation

HRID 2207719 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[C:7]2[CH:12]=[O:13].P(O)(O)([O-])=[O:15].[Na+].Cl([O-])=O.[Na+].[O-]S([O-])(=S)=O.[Na+].[Na+]>C1COCC1.O>[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[C:7]2[C:12]([OH:15])=[O:13]

Participants

7

Reactant 4

HCID 24477Sodium ThiosulfateHCID 23668197Sodium ChloriteHCID 23672064Monosodium phosphateHCID 468357198-Bromoquinoline-4-carbaldehyde

Product 1

HCID 184143088-Bromoquinoline-4-carboxylic acidYield 94%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

As shown in step 9-iv of Scheme 9, to a stirred suspension of 8-bromoquinoline-4-carbaldehyde (531.4 g, 2.25 mol) in THF (4.8 L) was added water (4.8 L) and monosodium phosphate (491.1 g, 4.05 mol). The mixture was cooled to 5° C. and, keeping the reaction temperature below 15° C., sodium chlorite (534.4 g, 4.727 mol) was slowly added portionwise as a solid over about 1 hour. After addition was complete the reaction mixture was stirred at 10° C. for 1 hour followed by the portionwise addition of 1N Na2S2O3 (1.18 L) whilst keeping the temperature below 20° C. The reaction mixture was stirred at RT followed by the removal of the THF under reduced pressure. The resulting aqueous solution containing a precipitate was treated with sat'd NaHCO3 (about 1 L) until a pH of 3 to 4 was achieved. This mixture was stirred an additional 15 minutes and the solid was collected by filtration, washed with water (2×1 L), washed with tert butyl methyl ether (2×500 mL), and dried in a convection oven at 60° C. for 48 hours. Additional drying under high vacuum provided 8-bromoquinoline-4-carboxylic acid (compound 2032, 530.7 g, 94% yield from compound 1030) as a yellowish tan solid: LC-MS=252.34 (M+H); 1H NMR (300 MHz, DMSO-d6) δ 14.09 (s, 1H), 9.16 (d, J=4.4 Hz, 1H), 8.71 (dd, J=8.6, 1.2 Hz, 1H), 8.25 (dd, J=7.5, 1.2 Hz, 1H), 8.03 (d, J=4.4 Hz, 1H), 7.64 (dd, J=8.6, 7.5 Hz, 1H).

Workup

  1. additionwas slowly added portionwise as a solid over about 1 hour
  2. additionAfter addition
  3. customthe temperature below 20° C
  4. stirringThe reaction mixture was stirred at RT
  5. customfollowed by the removal of the THF under reduced pressure
  6. additionThe resulting aqueous solution containing a precipitate
  7. additionwas treated with sat'd NaHCO3 (about 1 L) until a pH of 3 to 4
  8. stirringThis mixture was stirred an additional 15 minutes
  9. filtrationthe solid was collected by filtration
  10. washwashed with water (2×1 L)
  11. washwashed with tert butyl methyl ether (2×500 mL)
  12. customdried in a convection oven at 60° C. for 48 hours
  13. customAdditional drying under high vacuum

Sources & evidence

ORD record
ord-5a3d727959c54347a366cfa0f99b606d
Source dataset
uspto-grants-2016_06
Patent number
US09376448B2

Reaction notes

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