Sodium Hydroxide → 1-{2-[3-(2-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylic acid

HRID 1942745Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1942745
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:13][C:14]([C:17]3[C:18]([CH2:36][CH3:37])=[C:19]([CH2:23][CH2:24][N:25]4[CH2:30][CH2:29][CH:28]([C:31]([O:33]CC)=[O:32])[CH2:27][CH2:26]4)[CH:20]=[CH:21][CH:22]=3)=[CH:15][N:16]=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:13][C:14]([C:17]3[C:18]([CH2:36][CH3:37])=[C:19]([CH2:23][CH2:24][N:25]4[CH2:26][CH2:27][CH:28]([C:31]([OH:33])=[O:32])[CH2:29][CH2:30]4)[CH:20]=[CH:21][CH:22]=3)=[CH:15][N:16]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]

Komponenten

5

Edukt 2

HCID 14798Sodium HydroxideHCID 58494013Ethyl 1-{2-[3-(2-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylate

Produkt 1

HCID 545771561-{2-[3-(2-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylic acidAusbeute 15,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittel2×HCID 3776IsopropanolLösungsmittel

Versuchsvorschrift

To a solution of ethyl 1-{2-[3-(2-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylate (D89) (120 mg) in isopropanol (40 mL) and water (10 mL) stirred under nitrogen at room temperature was added a solution of NaOH (17.7 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-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylic acid (E40) (18 mg) as a TFA salt (white solid). δH (DMSO-d6, 400 MHz): 1.11 (3H, t), 1.34 (6H, d), 1.76 (2H, m), 2.11 (2H, m), 2.71 (2H, m), 3.07 (4H, m), 3.27 (2H, m), 3.53 (1H, m), 3.67 (2H, m), 4.80 (1H, m), 7.33 (4H, m), 7.82 (1H, s), 7.87 (1H, dd), 7.99 (1H, d), 9.29 (1H, br s), 12.59 (1H, br s). δF (DMSO-d6, 376 MHz): −73.5. MS (ES): C28H33ClN2O3S requires 512. found 513.1 (M+H+).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-13e9f1f472104c9c8ccdec42f98916fb
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08389508B2

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