Hydrochloric Acid → HCID 20664106, compound

HRID 1068248Notes

Reaction equation

HRID 1068248 reaction equation
[CH2:1]([C:8]1[S:9][C:10]([CH:15]2[CH2:20][CH2:19][N:18]([CH2:21][C@@H:22]3[C@@H:26]([C:27]4[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[CH:28]=4)[CH2:25][N:24]([CH2:34][C:35]([O:37]C)=[O:36])[CH2:23]3)[CH2:17][CH2:16]2)=[C:11]([CH2:13][CH3:14])[N:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].Cl>CO>[CH2:1]([C:8]1[S:9][C:10]([CH:15]2[CH2:16][CH2:17][N:18]([CH2:21][C@@H:22]3[C@@H:26]([C:27]4[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[CH:28]=4)[CH2:25][N:24]([CH2:34][C:35]([OH:37])=[O:36])[CH2:23]3)[CH2:19][CH2:20]2)=[C:11]([CH2:13][CH3:14])[N:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 86757036HCID 86757036, compound

Product 1

HCID 20664106HCID 20664106, compoundYield 93.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 23 mg (0.043 mmol) of (3-(S)-((4-(2-benzyl-4-ethyl-thiazol-5-yl)-piperidine-1-yl)methyl)-4-(S)-3-fluorophenylpyrrolidin-1-yl)-acetic acid, methyl ester in 1 mL of MeOH was treated with 0.1 mL of 1N NaOH. After stirring for 1 hr, another 0.1 mL of 1N NaOH was added and the reaction was heated in a 50° C. bath. After 1.5 hr at 50° C., the solution was cooled and neutralized to pH 7 with 1.2 N HCl. The solution was extracted with EtOAc and the EtOAc layer was washed with brine and dried. After concentration of the filtrate, the residue was purified on a Varian SCX ion exchange column using 2N NH3 in MeOH to elute the product. The isolated free base after concentration of the solution was treated with 1N HCl in Et2O and removal of solvent in vacuo furnished 21 mg of the title compound as a triHCl salt. Mass spec. 522.2 (M+1), HPLC A 1.99 min.

Workup

  1. waitAfter 1.5 hr at 50° C.
  2. temperaturethe solution was cooled
  3. extractionThe solution was extracted with EtOAc
  4. washthe EtOAc layer was washed with brine
  5. customdried
  6. customAfter concentration of the filtrate, the residue was purified on a Varian SCX ion exchange column
  7. washto elute the product
  8. additionThe isolated free base after concentration of the solution was treated with 1N HCl in Et2O and removal of solvent in vacuo

Sources & evidence

ORD record
ord-3a05d90a40634bbeb1378d4a23c01a60
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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