Sodium Hydroxide → HCID 54576940, compound

HRID 1942743Notes

Reaction equation

HRID 1942743 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[S:14][C:15]([C:18]3[C:19]([CH2:37][CH3:38])=[C:20]([CH2:24][CH2:25][N:26]4[CH2:31][CH2:30][CH:29]([C:32]([O:34]CC)=[O:33])[CH2:28][CH2:27]4)[CH:21]=[CH:22][CH:23]=3)=[CH:16][N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2].[OH-].[Na+]>C(O)(C)C.O>[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[S:14][C:15]([C:18]3[C:19]([CH2:37][CH3:38])=[C:20]([CH2:24][CH2:25][N:26]4[CH2:27][CH2:28][CH:29]([C:32]([OH:34])=[O:33])[CH2:30][CH2:31]4)[CH:21]=[CH:22][CH:23]=3)=[CH:16][N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:11])[CH3:12])#[N:2]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 66981746Ethyl 1-{2-[3-(2-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylate

Product 1

HCID 54576940HCID 54576940, compoundYield 24.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 3776IsopropanolSolvent

Procedure

To a solution of ethyl 1-{2-[3-(2-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylate (D86) (204 mg) in isopropanol (40 mL) and water (10 mL) stirred under nitrogen at room temperature was added a solution of NaOH (30.7 mg) in water in one charge. The reaction mixture was stirred at room temperature overnight. 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-[3-(2-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylic acid (E37) (48 mg) as a TFA salt (white solid). δH (DMSO-d6, 400 MHz): 1.10 (3H, t), 1.36 (6H, d), 1.76 (2H, m), 2.13 (2H, m), 2.72 (2H, m), 3.07 (4H, m), 3.28 (3H, m), 3.67 (2H, m), 4.91 (1H, m), 7.34 (3H, m), 7.44 (1H, d), 7.85 (1H, s), 8.22 (1H, dd), 8.28 (1H, d), 9.37 (1H, br s), 12.60 (1H, br s). δF (DMSO-d6, 376 MHz): −73.5. MS (ES): C29H33N3O3S requires 503. found 504.1 (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-63a06c06f431436991a6f4848b6220b1
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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