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

HRID 1942766Notes

Reaction equation

HRID 1942766 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]([CH2:37][CH3:38])=[C:19]([CH2:23][CH:24]4[CH2:29][CH2:28][N:27]([CH2:30][CH2:31][C:32]([O:34]CC)=[O:33])[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]([CH2:37][CH3:38])=[C:19]([CH2:23][CH:24]4[CH2:25][CH2:26][N:27]([CH2:30][CH2:31][C:32]([OH:34])=[O:33])[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 58494103Ethyl 3-(4-{[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]methyl}-1-piperidinyl)propanoate

Product 1

HCID 584941463-(4-{[3-(5-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]methyl}-1-piperidinyl)propanoic acidYield 13.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of ethyl 3-(4-{[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]methyl}-1-piperidinyl)propanoate (D141) (0.63 g, 1.133 mmol) in Isopropanol (5 mL) and Water (5.00 mL) was added NaOH (2.266 mL, 1.133 mmol). The reaction solution was heated to 90° C. for 1 hour. The solvent was evaporated in vacuo and the residue was acidified to pH=2-3, extracted with ethyl acetate, washed with water, dried and purified by Mass Directed AutoPrep to afford 3-(4-{[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]methyl}-1-piperidinyl)propanoic acid (E106) (83 mg) as a TFA salt. δH (DMSO-d6, 400 MHz): 1.00 (3H, t), 1.28 (6H, d), 1.44 (2H, m), 1.72 (3H, m), 2.63 (4H, m), 2.83 (4H, m), 3.17 (4H, m), 4.79 (1H, m), 7.24 (2H, m), 7.32 (1H, d), 7.59 (1H, dd), 7.94 (1H, dd), 8.07 (1H, d). δF (DMSO-d6, 376 MHz): −73.5. MS (ES): C28H34ClN3O3S requires 527.2. found 528.1 (M+H+)

Workup

  1. customThe solvent was evaporated in vacuo
  2. extractionextracted with ethyl acetate
  3. washwashed with water
  4. customdried
  5. custompurified by Mass Directed AutoPrep

Sources & evidence

ORD record
ord-afc30020055a499f81d6694bed9cd2cc
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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