4-Toluenesulfonyl chloride → Methyl 5-bromo-8-(tosyloxy)-1,6-naphthyridine-7-carboxylate

HRID 897381Notes

Reaction equation

HRID 897381 reaction equation
C(N(CC)CC)C.[CH3:8][O:9][C:10]([C:12]1[C:21]([OH:22])=[C:20]2[C:15]([CH:16]=[CH:17][CH:18]=[N:19]2)=[C:14]([Br:23])[N:13]=1)=[O:11].[C:24]1([CH3:34])[CH:29]=[CH:28][C:27]([S:30](Cl)(=[O:32])=[O:31])=[CH:26][CH:25]=1>C(Cl)(Cl)Cl>[CH3:8][O:9][C:10]([C:12]1[C:21]([O:22][S:30]([C:27]2[CH:28]=[CH:29][C:24]([CH3:34])=[CH:25][CH:26]=2)(=[O:32])=[O:31])=[C:20]2[C:15]([CH:16]=[CH:17][CH:18]=[N:19]2)=[C:14]([Br:23])[N:13]=1)=[O:11]

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 22343006Methyl 5-bromo-8-hydroxy-1,6-naphthyridine-7-carboxylate

Product 1

HCID 11339571Methyl 5-bromo-8-(tosyloxy)-1,6-naphthyridine-7-carboxylateYield 97%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
35 °C

Procedure

Triethylamine (0.759 g, 7.50 mmol) was added to a suspension of 5-bromo-8-hydroxy-1,6-naphthyridine-7-carboxylic acid methyl ester (6, 1.415 g, 5.000 mmol) in chloroform (5 mL) over 5 min maintaining the temperature at 20-50° C. to give a yellow suspension. p-Toluenesulfonyl chloride (1.15 g, 6.00 mmol) was added over 5 min maintaining the temperature at 20-40° C. to give a yellow solution. The mixture was aged at 40° C. for 2 h during which a crystalline solid precipitated out of the mixture and the color faded (HPLC analysis indicated <0.5% starting material remaining). The mixture was cooled to 20° C. over 15 min. MeOH (10 mL) was added over 30 min then a 1:1 mixture of MeOH:water (10 mL) was added over 30 min. The mixture was cooled to −40° C. over 30 min and aged at −40° C. for 30 min. The cold mixture was filtered and the solid was washed with 1:1 MeOH:water (10 mL), MeOH (5 mL), MTBE (10 mL) and hexanes (10 mL) all at 10-20° C. The off-white crystalline solid was dried under a stream of nitrogen to provide 2.112 g (97% yield) of 5-bromo-8-(p-toluenesulfonyloxy)-1,6-naphthyridine-7-carboxylic acid methyl ester (7)

Workup

  1. customto give a yellow suspension
  2. temperaturemaintaining the temperature at 20-40° C.
  3. customto give a yellow solution
  4. customa crystalline solid precipitated out of the mixture
  5. temperatureThe mixture was cooled to 20° C. over 15 min
  6. additionMeOH (10 mL) was added over 30 min
  7. additiona 1:1 mixture of MeOH
  8. additionwater (10 mL) was added over 30 min
  9. temperatureThe mixture was cooled to −40° C. over 30 min
  10. waitaged at −40° C. for 30 min
  11. filtrationThe cold mixture was filtered
  12. washthe solid was washed with 1:1 MeOH
  13. customat 10-20° C
  14. customThe off-white crystalline solid was dried under a stream of nitrogen

Sources & evidence

ORD record
ord-c4a3c3b05efd4cd68255df486a46eb01
Source dataset
uspto-grants-2005_07
Patent number
US06921759B2

Reaction notes

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