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Diisopropylethylamine → (+/-)-Tert-butyl 1-[3-({cyclopentyl[4-(trifluoromethyl)phenyl]acetyl}-amino)benzyl]cyclopropanecarboxylate

HRID 1475659
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HRID 1475659 반응식
[CH:1]1([CH:6]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)[C:7](O)=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[NH2:40][C:41]1[CH:42]=[C:43]([CH:55]=[CH:56][CH:57]=1)[CH2:44][C:45]1([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[CH2:47][CH2:46]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[CH:1]1([CH:6]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:17])([F:18])[F:19])=[CH:12][CH:11]=2)[C:7]([NH:40][C:41]2[CH:42]=[C:43]([CH:55]=[CH:56][CH:57]=2)[CH2:44][C:45]2([C:48]([O:50][C:51]([CH3:54])([CH3:52])[CH3:53])=[O:49])[CH2:47][CH2:46]2)=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2]1
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8

반응물 5

HCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58136514tert-Butyl 1-(3-aminobenzyl)cyclopropanecarboxylateHCID 67078122(+/-)-Cyclopentyl[4-(trifluoromethyl)phenyl]acetic acid

생성물 1

HCID 68170307
(+/-)-Tert-butyl 1-[3-({cyclopentyl[4-(trifluoromethyl)phenyl]acetyl}-amino)benzyl]cyclopropanecarboxylate

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매2회

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온도
0 °C

실험 절차

3.0 g (11.02 mmol) of (+/−)-cyclopentyl[4-(trifluoromethyl)phenyl]acetic acid were dissolved in 16.0 ml of DMF, and 1.79 g (13.22 mmol) of 1-hydroxy-1H-benzotriazole hydrate were added. The mixture was cooled to 0° C., and 3.8 ml (22.04 mmol) of N,N-diisopropylethylamine and 3.41 g (13.77 mmol) of tert-butyl 1-(3-aminobenzyl)cyclopropanecarboxylate, dissolved in a little DMF, were added. 5.03 g (13.22 mmol) of HATU were then added in several portions, and the reaction mixture was slowly warmed to RT and then stirred at RT for 3 h. The reaction was then added to water. After phase separation, the aqueous phase was extracted three times with ethyl acetate, and the combined organic phases were washed with saturated sodium chloride solution, dried over magnesium sulphate and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 20:1→10:1). This gave 4.89 g of the target compound (88.5% of theory).

후처리

  1. additionwere added
  2. temperaturethe reaction mixture was slowly warmed to RT
  3. customAfter phase separation
  4. extractionthe aqueous phase was extracted three times with ethyl acetate
  5. washthe combined organic phases were washed with saturated sodium chloride solution
  6. dry with materialdried over magnesium sulphate
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 20:1→10:1)

출처 및 근거

ORD 기록
ord-467231b685384fdea490742b933dfb17
출처 데이터셋
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09018258B2

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