Sodium Hydroxide → (4-{[3-(5-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]methyl}-1-piperidinyl)acetic acid

HRID 1942765Notes

Reaction equation

HRID 1942765 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:16][N:15]=[C:14]([C:17]3[C:18]([CH2:36][CH3:37])=[C:19]([CH2:23][CH:24]4[CH2:29][CH2:28][N:27]([CH2:30][C:31]([O:33]CC)=[O:32])[CH2:26][CH2:25]4)[CH:20]=[CH:21][CH:22]=3)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[OH-].[Na+]>C(O)(C)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:16][N:15]=[C:14]([C:17]3[C:18]([CH2:36][CH3:37])=[C:19]([CH2:23][CH:24]4[CH2:25][CH2:26][N:27]([CH2:30][C:31]([OH:33])=[O:32])[CH2:28][CH2:29]4)[CH:20]=[CH:21][CH:22]=3)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 58494152HCID 58494152, compound

Product 1

HCID 58494116(4-{[3-(5-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]methyl}-1-piperidinyl)acetic acidYield 77.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of ethyl (4-{[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]methyl}-1-piperidinyl)acetate (D145) (80 mg, 0.148 mmol) in Isopropanol (6 mL) and Water (6.00 mL) was added NaOH (1.476 mL, 0.738 mmol). The reaction solution was heated to 90° C. for 2 hours. The solvent was removed in vacuo and the residue was acidified to pH=3-4, extracted with ethyl acetate. The combined organic phases were dried, concentrated and purified by Mass Directed AutoPrep to afford (4-{[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]methyl}-1-piperidinyl)acetic acid (E105) (59 mg) as a TFA salt. δH (DMSO-d6, 400 MHz): 1.01 (3H, t), 1.28 (6H, d), 1.55 (2H, m), 1.72 (3H, m), 2.62 (2H, d), 2.87 (4H, m), 3.38 (2H, m), 3.98 (2H, s), 4.79 (1H, m), 7.23 (2H, m), 7.32 (1H, d), 7.59 (1H, dd), 7.95 (1H, dd), 8.07 (1H, d). δF (DMSO-d6, 376 MHz): −73.5. MS (ES): C27H32ClN3O3S requires 513.2. found 514.2 (M+H+).

Workup

  1. customThe solvent was removed in vacuo
  2. extractionextracted with ethyl acetate
  3. customThe combined organic phases were dried
  4. concentrationconcentrated
  5. custompurified by Mass Directed AutoPrep

Sources & evidence

ORD record
ord-6633b5ccfe2a4d2ea4dfbb32706751bc
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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