2-Mercaptobenzoic Acid → HCID 24703280, compound

HRID 1288937Notes

Reaction equation

HRID 1288937 reaction equation
[CH:1]1[CH:6]=[C:5]([C:7]([OH:9])=[O:8])[C:4]([SH:10])=[CH:3][CH:2]=1.C(=O)(O)[O-].[Na+].Cl[C:17]1[C:22]([N+:23]([O-:25])=[O:24])=[CH:21][CH:20]=[CH:19][N:18]=1>C(O)C.O.C(OCC)(=O)C>[N+:23]([C:22]1[C:17]([S:10][C:4]2[CH:3]=[CH:2][CH:1]=[CH:6][C:5]=2[C:7]([OH:9])=[O:8])=[N:18][CH:19]=[CH:20][CH:21]=1)([O-:25])=[O:24]

Participants

7

Reactant 3

HCID 54432-Mercaptobenzoic AcidHCID 796132-Chloro-3-nitropyridineHCID 516892Sodium Bicarbonate

Product 1

HCID 24703280HCID 24703280, compoundYield 71.7%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 11.67 g of 2-thiobenzoic acid in a mixture of 32 ml of ethanol and 11 ml of water is added portionwise 12.72 g of solid sodium bicarbonate. After the complete addition, the mixture is stirred for 15 minutes and 10.0 g of 2-chloro-3-nitropyridine added portionwise. The mixture is refluxed for 2 hours, cooled and then concentrated in vacuo. The residual aqueous solution is diluted with 15 ml of water, acidified with 2N HCl and extracted twice with 250 ml of ethyl acetate. The extract is concentrated under vacuum to give a yellow solid residue. The residue is dissolved in a minimum of ethyl acetate by heating on a steam bath. The solution is cooled overnight and filtered. (2.5 g of starting material). The filtrate is concentrated, chilled and filtered to give 12.5 g of 2-(3-nitro-2-pyridinylthio)benzoic acid as a yellow solid. The preceding compound (5.0 g) and 0.75 g of Pd/C in 60 ml of ethanol is shaken in a Parr hydrogenator under 45 psi of hydrogen for 18 hours. The mixture is filtered through diatmoaceous earth and the filter cake washed with 200 ml of dichloromethane. The combined filtrate is evaporated in vacuo to give a solid. The solid is triturated with ethanol and filtered to give 3.6 g of yellow solid. This solid (3.0 g) is again hydrogenated with Pd/c (0.50 g) in 50 ml of ethanol and 30 ml of acetic acid under 45 psi of hydrogen for 18 hours. The mixture is filtered through diatomaceous earth and the filter cake washed with methanol. The combined filtrate is concentrated in vacuo to give 1.6 g of solid. This solid in 25 ml of N,N-dimethylformamide is again reduced with 0.80 g of Pd/C under 45 psi of hydrogen to give 0.57 g of solid. Recrystalization from ethyl acetate gives 0.28 g of 2-(3-amino-2-pyridinylthio)benzoic acid. The preceding compound (0.20 g) is heated in 2-hydroxypyridine at 170° C. to give 5,6-dihydropyrido[2,3-b][1,4]benzothiazepine as a yellow solid. The preceding compound is reacted with borane-dimethylsulfide as described for Reference Example 17 to give the product as a solid.

Workup

  1. additionAfter the complete addition
  2. temperatureThe mixture is refluxed for 2 hours
  3. temperaturecooled
  4. concentrationconcentrated in vacuo
  5. additionThe residual aqueous solution is diluted with 15 ml of water
  6. extractionextracted twice with 250 ml of ethyl acetate
  7. concentrationThe extract is concentrated under vacuum
  8. customto give a yellow solid residue
  9. temperatureby heating on a steam bath
  10. temperatureThe solution is cooled overnight
  11. filtrationfiltered
  12. concentrationThe filtrate is concentrated
  13. temperaturechilled
  14. filtrationfiltered

Sources & evidence

ORD record
ord-4d0888eada694d0291171ea5b1993d6c
Source dataset
uspto-grants-1998_05
Patent number
US05747487

Reaction notes

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