Hydrochloric Acid → 6-Methanesulfonamidopyridine-3-carboxylic acid

HRID 881866Notes

Reaction equation

HRID 881866 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8]C)=[O:7])=[CH:4][N:3]=1.[CH3:12][S:13](Cl)(=[O:15])=[O:14].[OH-].[Na+].Cl>C(Cl)Cl>[CH3:12][S:13]([NH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=1)(=[O:15])=[O:14]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 31297Methanesulfonyl chlorideHCID 737487Methyl 6-aminonicotinate

Product 1

HCID 587956276-Methanesulfonamidopyridine-3-carboxylic acidYield 29.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of methyl 6-aminonicotinate (1.0 g, 6.57 mmol) in CH2Cl2 (50 mL) with TEA (0.96 mL, 6.90 mmol) cooled in an ice bath is added MsCl (0.54 mL, 6.90 mmol) slowly. The crude is allowed to stir at room temperature for 2 hrs. The crude is then concentrated. The crude is dissolved in MeOH (20 mL) and to the crude is added 1 N NaOH (30 mL, 30 mmol). The crude is stirred at room temperature for 18 hrs. The crude is quenched with 1N HCl (32 mL, 32 mmol). The crude is concentrated to remove MeOH and some water is removed as well. The crude is diluted in CH2Cl2 and basified with 1 N NaOH (30 mL). The aq. layer is extracted with CH2Cl2. The aq. layer is acidified with concentrated HCl to bring the PH to 1 via PH paper indicator. The crude is diluted in EtOAc and the aq. layer is extracted with EtOAc. The combined organic layer is washed with brine, dried over MgSO4, filtered, and concentrated to give 6-(methylsulfonamido)nicotinic acid (421 mg) as a yellow solid. HPLC retention time=0.40 minutes (condition D); MS (m+1)=217.2.

Workup

  1. concentrationThe crude is then concentrated
  2. dissolutionThe crude is dissolved in MeOH (20 mL) and to the crude
  3. stirringThe crude is stirred at room temperature for 18 hrs
  4. concentrationThe crude is concentrated
  5. customto remove MeOH
  6. customsome water is removed as well
  7. additionThe crude is diluted in CH2Cl2
  8. extractionThe aq. layer is extracted with CH2Cl2
  9. additionThe crude is diluted in EtOAc
  10. extractionthe aq. layer is extracted with EtOAc
  11. washThe combined organic layer is washed with brine
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-09f79495ecc543f2beed4455e153c062
Source dataset
uspto-grants-2015_03
Patent number
US08993631B2

Reaction notes

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