Water → 4-(2-Methylpiperidin-1-yl)-3-[(methylsulfonyl)amino]benzoic acid

HRID 400752Notes

Reaction equation

HRID 400752 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[NH2:6][C:7]1[CH:8]=[C:9]([CH:15]=[CH:16][C:17]=1[N:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH:19]1[CH3:24])[C:10]([O:12]CC)=[O:11].[OH-].[Li+].O>C(Cl)Cl.C1COCC1>[CH3:24][CH:19]1[CH2:20][CH2:21][CH2:22][CH2:23][N:18]1[C:17]1[CH:16]=[CH:15][C:9]([C:10]([OH:12])=[O:11])=[CH:8][C:7]=1[NH:6][S:2]([CH3:1])(=[O:4])=[O:3]

Participants

7

Reactant 4

HCID 962WaterHCID 3939Lithium HydroxideHCID 31297Methanesulfonyl chlorideHCID 56828460Ethyl 3-amino-4-(2-methylpiperidin-1-yl)benzoate

Product 1

HCID 584433444-(2-Methylpiperidin-1-yl)-3-[(methylsulfonyl)amino]benzoic acidYield 88.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methanesulfonyl chloride (1.68 mL; 21.72 mmol) was added dropwise (addition took 5 min) to a cold (0° C.) solution of Py (10 mL) and ethyl 3-amino-4-(2-methylpiperidin-1-yl)benzoate (5.18 g; 19.74 mmol) in DCM (40 mL) and the reaction mixture was allowed to return to RT over one hour. The reaction mixture was stirred at RT for 3 hours. After this time, it was concentrated and the residue was taken up in water. The aqueous phase was extracted with EtOAc. The combined organic phases were washed with HCl (1 M) then brine, dried over MgSO4 and concentrated giving a yellow oil. This oil was taken up in THF (30 mL) and lithium hydroxide (2.36 g; 98.72 mmol) was added, followed by water (30 mL). The resulting mixture was stirred at RT for 2 days. THF was removed under vacuum and the solution diluted with water. This solution was washed with Et2O and acidified to pH 2 with conc HCl. The aqueous phase was extracted with EtOAc, washed with brine, dried over MgSO4 and concentrated affording the title compound as a beige solid (5.48 g, 88%). 1H NMR (DMSO-d6) δ 12.98 (br s, 1H), 8.53 (br s, 1H), 8.07-8.06 (d, J=1.91 Hz, 1H), 7.77-7.73 (dd, J=8.34 Hz, 1.97 Hz, 1H), 7.47-7.45 (d, J=8.34 Hz, 1H), 3.43-2.58 (m, 6H), 1.84-1.46 (m, 6H), 0.83-0.81 (d, J=6.09 Hz, 3H). HPLC (Method A) Rt 2.29 min (Purity: 99.0%).

Workup

  1. concentrationAfter this time, it was concentrated
  2. extractionThe aqueous phase was extracted with EtOAc
  3. washThe combined organic phases were washed with HCl (1 M)
  4. dry with materialbrine, dried over MgSO4
  5. concentrationconcentrated
  6. customgiving a yellow oil
  7. stirringThe resulting mixture was stirred at RT for 2 days
  8. customTHF was removed under vacuum
  9. additionthe solution diluted with water
  10. washThis solution was washed with Et2O
  11. extractionThe aqueous phase was extracted with EtOAc
  12. washwashed with brine
  13. dry with materialdried over MgSO4
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-283ed5f578e944208faef3f37529f647
Source dataset
uspto-grants-2014_06
Patent number
US08741923B2

Reaction notes

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