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

HRID 1172184ノート

反応式

HRID 1172184 の反応式
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]

参加物

4

反応物 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 57917724HCID 57917724、化合物

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-dde3087af1314e9b82d109dedc9994e0
出典データセット
uspto-grants-2010_11
特許番号
US07834004B2

反応ノート

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