Citric Acid → Tert-butyl 4-[2-(4-{[(tert-butoxycarbonyl)(1,3-thiazol-4-yl)amino]sulfonyl}-2-chloro-5-fluorophenoxy)-5-chlorophenyl]piperidine-1-carboxylate

HRID 46232

Reaktionsgleichung

Reaktionsgleichung von HRID 46232
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:21])=[C:6]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[Cl:28][C:29]1[C:30](F)=[CH:31][C:32]([F:51])=[C:33]([S:35]([N:38]([C:46]2[N:47]=[CH:48][S:49][CH:50]=2)[C:39](=[O:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42])(=[O:37])=[O:36])[CH:34]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CS(C)=O.C(OCC)(=O)C.O>[C:41]([O:40][C:39]([N:38]([C:46]1[N:47]=[CH:48][S:49][CH:50]=1)[S:35]([C:33]1[C:32]([F:51])=[CH:31][C:30]([O:21][C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][C:6]=2[CH:8]2[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:15])[CH2:12][CH2:13]2)=[C:29]([Cl:28])[CH:34]=1)(=[O:37])=[O:36])=[O:45])([CH3:44])([CH3:42])[CH3:43]

Komponenten

8

Edukt 4

HCID 311Citric AcidHCID 11430Potassium CarbonateHCID 59436559Tert-butyl4-(5-chloro-2-hydroxyphenyl)piperidine-1-carboxylateHCID 59436581Tert-butyl (5-chloro-2,4-difluorophenyl)sulfonyl(thiazol-4-yl)carbamate

Produkt 1

HCID 66905633Tert-butyl 4-[2-(4-{[(tert-butoxycarbonyl)(1,3-thiazol-4-yl)amino]sulfonyl}-2-chloro-5-fluorophenoxy)-5-chlorophenyl]piperidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 679Dimethyl SulfoxideLösungsmittelHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Example 655 from above can be made as follows. To a solution of tert-butyl 4-(5-chloro-2-hydroxyphenyl)piperidine-1-carboxylate (Preparation 231, 38 mg, 0.122 mmol) and potassium carbonate (50.6 mg, 0.366 mmol) in dimethyl sulfoxide (1 mL) was added tert-butyl [(5-chloro-2,4-difluorophenyl)sulfonyl]1,3-thiazol-4-ylcarbamate (Preparation 453, 50 mg, 0.122 mmol). The mixture was stirred at room temperature for 16 hours before diluting with ethyl acetate (10 mL) and water (10 mL). The aqueous phase was acidified to pH 4 with saturated citric acid solution (aqueous) and extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with saturated aqueous sodium chloride solution (30 mL), dried over sodium sulphate, filtered and concentrated in vacuo to afford tert-butyl 4-[2-(4-{[(tert-butoxycarbonyl)(1,3-thiazol-4-yl)amino]sulfonyl}-2-chloro-5-fluorophenoxy)-5-chlorophenyl]piperidine-1-carboxylate as a white foam. This was dissolved in dichloromethane (1 mL), trifluoroacetic acid added (200 μL) and reaction stirred for 16 hours at room temperature before concentrating in vacuo. Purification by preparative HPLC afforded the title compound.

Aufarbeitung

  1. extractionextracted with ethyl acetate (3×10 mL)
  2. washThe combined organic layers were washed with saturated aqueous sodium chloride solution (30 mL)
  3. dry with materialdried over sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-1e55bfae5d094510ac63053323fafbde
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08541588B2

Verknüpfte Notizen

Wird geladen…