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

HRID 1727063노트

반응식

HRID 1727063 반응식
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]

참가 물질

4

반응물 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 57917724HCID 57917724, 화합물

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-d221a5dad2a74ddfb79e83d31dffae20
출처 데이터셋
uspto-grants-2009_02
특허 번호
US07494999B2

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