Lithium hydroxide, monohydrate → QX28Nxx8UG

HRID 23795Notes

Reaction equation

HRID 23795 reaction equation
C([O:3][C:4](=[O:37])[C:5]([C:8]1[CH:13]=[CH:12][C:11]([CH2:14][N:15]([CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH2:33][C:34]([OH:36])=[O:35])[CH:27]=2)[S:16]([C:19]2[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=2)(=[O:18])=[O:17])=[CH:10][CH:9]=1)([CH3:7])[CH3:6])C.O[Li].O>C1COCC1.O>[C:34]([CH2:33][O:32][C:28]1[CH:27]=[C:26]([CH:31]=[CH:30][CH:29]=1)[CH2:25][N:15]([CH2:14][C:11]1[CH:12]=[CH:13][C:8]([C:5]([CH3:7])([CH3:6])[C:4]([OH:37])=[O:3])=[CH:9][CH:10]=1)[S:16]([C:19]1[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=1)(=[O:18])=[O:17])([OH:36])=[O:35]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrate2×HCID 697316782-(4-{[(3-Carboxymethoxy-benzyl)-(pyridine-3-sulfonyl)-amino]-methyl}-phenyl)-2-methyl-propionic Acid Ethyl Ester

Product 1

HCID 10174435QX28Nxx8UGYield 94.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(4-{[(3-carboxymethoxy-benzyl)-(pyridine-3-sulfonyl)-amino]-methyl}-phenyl)-2-methyl-propionic acid ethyl ester (83 mg, 0.157 mmol) in THF (10 mL) was added water (1 mL) and LiOH.H2O (66 mg, 1.58 mmol). The reaction was heated at reflux for 24 h. Additional LiOH.H2O (66 mg, 1.58 mmol) in water (2 mL) was added and the reaction was heated at reflux for 30 h. The mixture was concentrated in vacuo and to the residue was added THF (3 mL) and water (1.5 mL). The reaction was heated at reflux for 24 h and was cooled to room temperature. The solution was diluted with water and the pH was adjusted to about 5 by addition of 1N HCl. Sodium chloride was added and the aqueous solution was washed with EtOAc (3×). The combined organic solutions were dried (MgSO4), filtered, and concentrated to provide the title compound (74 mg). 1H NMR (400 MHz, CDCl3) δ 8.94 (s, 1H), 8.73 (s, 1H), 8.13 (d, 1H), 7.55 (m, 1H), 7.23 (d, 2H), 7.11 (m, 3H), 6.78 (d, 1H), 6.73 (d, 1H), 6.68 (s, 1H), 4.90 (s, 2H), 4.39 (s, 2H), 3.30 (s, 2H), 1.50 (s, 6H); MS 497 (M−1).

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 24 h
  3. temperaturethe reaction was heated
  4. temperatureat reflux for 30 h
  5. concentrationThe mixture was concentrated in vacuo and to the residue
  6. additionwas added THF (3 mL) and water (1.5 mL)
  7. temperatureThe reaction was heated
  8. temperatureat reflux for 24 h
  9. additionThe solution was diluted with water
  10. additionthe pH was adjusted to about 5 by addition of 1N HCl
  11. additionSodium chloride was added
  12. washthe aqueous solution was washed with EtOAc (3×)
  13. dry with materialThe combined organic solutions were dried (MgSO4)
  14. filtrationfiltered
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-8d37fafa44e7460d90f98534c4ded948
Source dataset
uspto-grants-2005_02
Patent number
US06852863B2

Reaction notes

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