Trifluoroacetic acid methylene chloride → (r)-4-(5-Trifluoromethyl-pyridin-2-yl)-piperazine-2-carboxylic acid methyl ester

HRID 1727063Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1727063
COC([CH:5]1[N:10]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][N:12]=2)[CH2:9][CH2:8][N:7](C(OC(C)(C)C)=O)[CH2:6]1)=O.[C:28]([OH:34])(C(F)(F)F)=[O:29].[CH2:35](Cl)Cl>C(Cl)Cl>[CH3:35][O:34][C:28]([C@H:6]1[CH2:5][N:10]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:18])([F:19])[F:20])=[CH:13][N:12]=2)[CH2:9][CH2:8][NH:7]1)=[O:29]

Komponenten

4

Edukt 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 57917724HCID 57917724, Verbindung

Produkt 1

HCID 67045817(r)-4-(5-Trifluoromethyl-pyridin-2-yl)-piperazine-2-carboxylic acid methyl esterAusbeute 94 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

4-(5-Trifluoromethyl-pyridin-2-yl)-piperazine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (110 mg, 0.28 mmol) was combined with 2.0 mL of 25% TFA/CH2Cl2 and was stirred at room temperature for 30 min. After this period the reaction mixture was diluted with CH2Cl2 (25 mL) and was washed with sat'd NaHCO3 (2×10 mL) and brine. The resulting CH2Cl2 layer was dried over anhydrous Na2SO4 and was evaporated in vacuo to yield crude amine. The crude amine was purified using flash silica chromatography (0-10% MeOH/CH2Cl2) to yield 77 mg (94%) of (R)-4-(5-trifluoromethyl-pyridin-2-yl)-piperazine-2-carboxylic acid methyl ester as a yellow residue. This material was combined with 6-Chlorosulfonyl-indan-1-carboxylic acid 4-nitro-benzyl ester from Step 2 (102 mg, 0.27 mmoles) and triethylamine (46 μL, 0.33 mmol) in 2.0 mL of anhydrous THF, and was stirred at 60° C. for 5 hours. After this period the reaction mixture was evaporated in vacuo and the resulting residue was combined with 30 mL of benzene. The resulting heterogeneous mixture was filtered with benzene washings. The filtrate was then evaporated in vacuo and purified using flash silica chromatography (0-30% EtOAc/Hexane) to yield 4-[3-(4-Nitro-benzyloxycarbonyl)-indane-5-sulfonyl]-1-(5-trifluoromethyl-pyridin-2-yl)-piperazine-2-carboxylic acid methyl ester.

Aufarbeitung

  1. washwas washed with sat'd NaHCO3 (2×10 mL) and brine
  2. dry with materialThe resulting CH2Cl2 layer was dried over anhydrous Na2SO4
  3. customwas evaporated in vacuo
  4. customto yield crude amine
  5. customThe crude amine was purified

Quellen und Nachweise

ORD-Eintrag
ord-d221a5dad2a74ddfb79e83d31dffae20
Quelldatensatz
uspto-grants-2009_02
Patentnummer
US07494999B2

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