Lithium Hydroxide → KD-3010

HRID 249700Notes

Reaction equation

HRID 249700 reaction equation
C[O:2][C:3]([C@@H:5]1[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][C:11]=2[S:14]([N:17]2[C@H:22]([CH3:23])[CH2:21][N:20]([C:24]3[CH:29]=[CH:28][C:27]([O:30][C:31]([F:34])([F:33])[F:32])=[CH:26][CH:25]=3)[CH2:19][C@@H:18]2[CH3:35])(=[O:16])=[O:15])[CH2:6]1)=[O:4].[OH-:36].[Li+].[CH2:38]1COCC1>O>[S:14]([C:11]1[CH:12]=[CH:7][C:8]([CH3:38])=[CH:9][CH:10]=1)([OH:15])(=[O:16])=[O:36].[CH3:35][C@H:18]1[CH2:19][N:20]([C:24]2[CH:25]=[CH:26][C:27]([O:30][C:31]([F:33])([F:32])[F:34])=[CH:28][CH:29]=2)[CH2:21][C@@H:22]([CH3:23])[N:17]1[S:14]([C:11]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:12]=1[CH2:13][C@@H:5]([C:3]([OH:4])=[O:2])[CH2:6]2)(=[O:15])=[O:16]

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 23728688HCID 23728688, compound

Product 1

HCID 16048651KD-3010

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of (S)-4-[cis-2,6-dimethyl-4-(4-trifluoromethoxy-phenyl)-piperazine-1-sulfonyl]-indan-2-carboxylic acid methyl ester, in THF, is added a solution of lithium hydroxide in water, which is stirred at 20° C. and concentrated under reduced pressure. The reaction mixture is cooled to 9° C., neutralized with 32% HCl, and extracted from toluene. Water is removed from the organic solution by azeotropic distillation. Following distillation, the organic solution is cooled to ambient temperature and transferred to a feeding vessel. The reactor is charged with p-toluenesulfonic acid in toluene and water is removed by azeotropic distillation. The solution is cooled to 60° C., followed by the addition of the organic solution from the feeding vessel. The mixture is stirred at 83° C., then cooled to 10° C. to induce crystallization. The product suspension is filtered, the filter cake rinsed with heptane, and dried on a rotovap, at 40° C., to afford (S)-4-[cis-2,6-dimethyl-4-(4-trifluoromethoxy-phenyl)-piperazine-1-sulfonyl]-indan-2-carboxylic acid tosylate. 1HNMR δ 1.60 (d), 1.62 (d), 2.33 (s), 3.23 (m), 3.49 (m), 3.39 (m), 4.05 (m), 4.49 (m), 3.40 (dd), 3.23 (dd), 7.14 (d), 7.14 (d), 7.09 (d), 7.09 (d), 7.59 (d), 7.59 (d), 7.71 (d), 7.26, dd, 7.57 (d), 7.57 (d), 7.40 (d).

Workup

  1. concentrationconcentrated under reduced pressure
  2. temperatureThe reaction mixture is cooled to 9° C.
  3. extractionextracted from toluene
  4. customWater is removed from the organic solution by azeotropic distillation
  5. distillationdistillation
  6. temperaturethe organic solution is cooled to ambient temperature
  7. customtransferred to a feeding vessel
  8. additionThe reactor is charged with p-toluenesulfonic acid in toluene and water
  9. customis removed by azeotropic distillation
  10. temperatureThe solution is cooled to 60° C.
  11. additionfollowed by the addition of the organic solution from the feeding vessel
  12. stirringThe mixture is stirred at 83° C.
  13. temperaturecooled to 10° C.
  14. customcrystallization
  15. filtrationThe product suspension is filtered
  16. washthe filter cake rinsed with heptane
  17. customdried on a rotovap, at 40° C.

Sources & evidence

ORD record
ord-6748016a65ab4fc0a560025f9a7407bd
Source dataset
uspto-grants-2011_01
Patent number
US07863276B2

Reaction notes

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