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1-Hydroxybenzotriazole hydrate → 1-t-Butoxycarbonyl-4-(1-(4-fluorophenyl)-2-{4-[4-(2-methoxynaphthalen-1-yl)butyl]piperazin-1-yl}-2-oxoethyl)piperidine

HRID 497338
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HRID 497338 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]([C:22](O)=[O:23])[C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.Cl.[CH3:27][O:28][C:29]1[CH:38]=[CH:37][C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:30]=1[CH2:39][CH2:40][CH2:41][CH2:42][N:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1.Cl.CNC(NC)CCN=C=NCC.O.ON1C2C=CC=CC=2N=N1>CN(C)C=O.C(OCC)(=O)C.C(N(CC)CC)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[C:22]([N:46]2[CH2:45][CH2:44][N:43]([CH2:42][CH2:41][CH2:40][CH2:39][C:30]3[C:31]4[C:36](=[CH:35][CH:34]=[CH:33][CH:32]=4)[CH:37]=[CH:38][C:29]=3[O:28][CH3:27])[CH2:48][CH2:47]2)=[O:23])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
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참가 물질

8

반응물 4

HCID 27960291-Hydroxybenzotriazole hydrateHCID 223186521-[4-(2-Methoxynaphthalen-1-yl)butyl]piperazine dihydrochlorideHCID 223186671-t-Butoxycarbonyl-4-[carboxy-(4-fluorophenyl)methyl]piperidineHCID 574299851-(3,3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride

생성물 1

HCID 223186381-t-Butoxycarbonyl-4-(1-(4-fluorophenyl)-2-{4-[4-(2-methoxynaphthalen-1-yl)butyl]piperazin-1-yl}-2-oxoethyl)piperidine
수율 72.1%

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 8471Triethylamine용매HCID 8857Ethyl Acetate용매

실험 절차

2.2 g of 1-t-Butoxycarbonyl-4-[carboxy-(4-fluorophenyl)methyl]piperidine was dissolved in 20 ml of dimethylformamide, and 2.0 g of 1-[4-(2-methoxynaphthalen-1-yl)butyl]piperazine dihydrochloride, 1.9 g of 1-(3,3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 1.9 g of 1-hydroxybenzotriazole monohydrate and 3.5 ml of triethylamine were added, followed by stirring at room temperature overnight. The reaction solution was diluted with ethyl acetate and washed with a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate. After removal of the drying agent by filtration, the filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (Chromatorex NH, hexane:ethyl acetate=3:1) to give 2.4 g of 1-t-butoxycarbonyl-4-(1-(4-fluorophenyl)-2-{4-[4-(2-methoxynaphthalen-1-yl)butyl]piperazin-1-yl}-2-oxoethyl)piperidine as an oil.

후처리

  1. washwashed with a saturated aqueous sodium bicarbonate solution
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. customAfter removal of the drying agent
  4. filtrationby filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe residue was purified by a silica gel column chromatography (Chromatorex NH, hexane:ethyl acetate=3:1)

출처 및 근거

ORD 기록
ord-fedcccc921904bc88708d4e6dafcac37
출처 데이터셋
uspto-grants-2005_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06949552B2

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