Sodium Hydroxide → 1-[(2-Ethyl-3-{2-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}phenyl)methyl]-4-piperidinecarboxylic acid

HRID 1942739Notes

Reaction equation

HRID 1942739 reaction equation
[CH2:1]([C:3]1[C:8]([C:9]2[S:13][C:12]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH:21]([CH3:23])[CH3:22])=[C:16]([C:24]([F:27])([F:26])[F:25])[CH:15]=3)=[N:11][CH:10]=2)=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:28][N:29]1[CH2:34][CH2:33][CH:32]([C:35]([O:37]CC)=[O:36])[CH2:31][CH2:30]1)[CH3:2].[OH-].[Na+]>C(O)(C)C.O>[CH2:1]([C:3]1[C:8]([C:9]2[S:13][C:12]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH:21]([CH3:23])[CH3:22])=[C:16]([C:24]([F:27])([F:25])[F:26])[CH:15]=3)=[N:11][CH:10]=2)=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:28][N:29]1[CH2:30][CH2:31][CH:32]([C:35]([OH:37])=[O:36])[CH2:33][CH2:34]1)[CH3:2]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 66981836Ethyl 1-[(2-ethyl-3-{2-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}phenyl)methyl]-4-piperidinecarboxylate

Product 1

HCID 545767231-[(2-Ethyl-3-{2-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}phenyl)methyl]-4-piperidinecarboxylic acidYield 18.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 3776IsopropanolSolvent

Procedure

To a solution of ethyl 1-[(2-ethyl-3-{2-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}phenyl)methyl]-4-piperidinecarboxylate (D81) (160 mg) in isopropanol (3 mL) and water (0.750 mL) stirred under nitrogen at room temperature was added a solution of NaOH (26.8 mg) in water in one charge. The reaction mixture was stirred at room temperature for 2 h. Isopropanol was removed in vacuo. The residue was dissolved in water and acidified with 1N HCl to pH=5. The solvent was removed in vacuo, the residue was dissolved in THF, and filtered. The filtrate was purified by Mass Directed AutoPrep to give 1-[(2-ethyl-3-{2-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}phenyl)methyl]-4-piperidinecarboxylic acid (E32) (28 mg). δH (DMSO-d6, 400 MHz): 1.07 (3H, t), 1.33 (6H, d), 1.53 (2H, m), 1.77 (2H, m), 2.03 (2H, m), 2.22 (1H, m), 2.77 (4H, m), 3.49 (2H, s), 4.89 (1H, m), 7.24 (1H, t), 7.30 (1H, d), 7.38 (1H, d), 7.44 (1H, d), 7.86 (1H, s), 8.15 (2H, m), 12.09 (1H, br s). δF (DMSO-d6, 376 MHz): −61.3. MS (ES): C28H31F3N2O3S requires 532. found 533.3 (M+H+).

Workup

  1. additioncharge
  2. customIsopropanol was removed in vacuo
  3. dissolutionThe residue was dissolved in water
  4. customThe solvent was removed in vacuo
  5. dissolutionthe residue was dissolved in THF
  6. filtrationfiltered
  7. customThe filtrate was purified by Mass Directed AutoPrep

Sources & evidence

ORD record
ord-d6e964e890ff43e7871e22f4dfd3ffac
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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