Acetic Acid → 1-Cyclopropylmethyl-4-[2-(3,3,5,5-tetramethylcyclohexyl)-4-thiazol-2-ylphenyl]piperazine

HRID 32243

Reaktionsgleichung

Reaktionsgleichung von HRID 32243
[CH3:1][C:2]1([CH3:27])[CH2:7][C:6]([CH3:9])([CH3:8])[CH2:5][CH:4]([C:10]2[CH:15]=[C:14]([C:16]3[S:17][CH:18]=[CH:19][N:20]=3)[CH:13]=[CH:12][C:11]=2[N:21]2[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)[CH2:3]1.[CH:28]1([CH:31]=O)[CH2:30][CH2:29]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.C(=O)([O-])O.[Na+]>C(OCC)(=O)C.O.O1CCCC1>[CH:28]1([CH2:31][N:24]2[CH2:25][CH2:26][N:21]([C:11]3[CH:12]=[CH:13][C:14]([C:16]4[S:17][CH:18]=[CH:19][N:20]=4)=[CH:15][C:10]=3[CH:4]3[CH2:3][C:2]([CH3:27])([CH3:1])[CH2:7][C:6]([CH3:8])([CH3:9])[CH2:5]3)[CH2:22][CH2:23]2)[CH2:30][CH2:29]1

Komponenten

9

Edukt 5

HCID 176Acetic AcidHCID 123114CyclopropanecarboxaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 231428281-[2-(3,3,5,5-Tetramethylcyclohexyl)-4-thiazol-2-ylphenyl]piperazine

Produkt 1

HCID 231415641-Cyclopropylmethyl-4-[2-(3,3,5,5-tetramethylcyclohexyl)-4-thiazol-2-ylphenyl]piperazine

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel2×

Versuchsvorschrift

To a mixture of 1-[2-(3,3,5,5-tetramethylcyclohexyl)-4-thiazol-2-ylphenyl]piperazine (15 mg, 0.039 mmol) produced in Example (99c), cyclopropanecarbaldehyde (0.006 mL, 0.080 mmol) and tetrahydrofuran (2 mL) were added sodium triacetoxyborohydride (21 mg, 0.099 mmol) and acetic acid (0.003 mL, 0.052 mmol) in that order, followed by stirring for 1 hour and 40 minutes at room temperature. Ethyl acetate, saturated aqueous solution of sodium hydrogencarbonate and water were added to the reaction mixture and extraction was performed with ethyl acetate. The separated organic layer was concentrated by blowing nitrogen. The resultant residue was purified by NH silica gel column chromatography (ethyl acetate/hexane) to give 1-cyclopropylmethyl-4-[2-(3,3,5,5-tetramethylcyclohexyl)-4-thiazol-2-ylphenyl]piperazine. This compound was dissolved in dichloromethane, and a 4N solution of hydrogen chloride in ethyl acetate was added. The solution was concentrated by blowing nitrogen, and then diethyl ether was added to the obtained residue to produce a solid, which was then triturated by sonication. The supernatant diethyl ether solution was removed, and the obtained solid residue was dried by blowing nitrogen, to give 16 mg of the title compound as a light yellow solid.

Aufarbeitung

  1. concentrationThe separated organic layer was concentrated
  2. customThe resultant residue was purified by NH silica gel column chromatography (ethyl acetate/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-ec6c22109443468a9617c92ee42d5ffe
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07425554B2

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