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1-Hydroxybenzotriazole → N-((1RS,2SR)-2-(4-fluorophenyl)-2-hydroxy-1-((4-methyl-3-((1,1,2,2-tetrafluoroethyl)oxy)phenyl)methyl)ethyl)-6,7-dihydro-5H-benzo[a]cycloheptene-1-carboxamide

HRID 1610534
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HRID 1610534 반응식
[NH2:1][CH:2]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([CH3:19])=[C:15]([O:20][C:21]([F:26])([F:25])[CH:22]([F:24])[F:23])[CH:14]=1)[CH:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1)[OH:4].[C:27]1([C:38](O)=[O:39])[CH:28]=[CH:29][CH:30]=[C:31]2[CH2:37][CH2:36][CH2:35][CH:34]=[CH:33][C:32]=12.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1>C(#N)C.O>[F:11][C:8]1[CH:9]=[CH:10][C:5]([CH:3]([OH:4])[CH:2]([NH:1][C:38]([C:27]2[CH:28]=[CH:29][CH:30]=[C:31]3[CH2:37][CH2:36][CH2:35][CH:34]=[CH:33][C:32]=23)=[O:39])[CH2:12][C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[C:15]([O:20][C:21]([F:26])([F:25])[CH:22]([F:24])[F:23])[CH:14]=2)=[CH:6][CH:7]=1
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참가 물질

7

반응물 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22261958(1RS,2SR)-2-amino-1-(4-fluorophenyl)-3-(4-methyl-3-((1,1,2,2-tetrafluoroethyl)oxy)phenyl)-1-propanolHCID 222620106,7-dihydro-5H-benzo[a]cycloheptene-1-carboxylic acid

생성물 1

HCID 22261554
N-((1RS,2SR)-2-(4-fluorophenyl)-2-hydroxy-1-((4-methyl-3-((1,1,2,2-tetrafluoroethyl)oxy)phenyl)methyl)ethyl)-6,7-dihydro-5H-benzo[a]cycloheptene-1-carboxamide
수율 83.2%

시약·촉매·용매 2

HCID 962Water용매HCID 6342Acetonitrile용매

실험 절차

To a solution of (1RS,2SR)-2-amino-1-(4-fluorophenyl)-3-(4-methyl-3-((1,1,2,2-tetrafluoroethyl)oxy)phenyl)-1-propanol (300 mg, 0.80 mmol) in acetonitrile (20 ml) were added 6,7-dihydro-5H-benzo[a]cycloheptene-1-carboxylic acid (150 mg, 0.80 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (230 mg, 1.20 mmol) and 1-hydroxy-1H-benzotriazole (123 mg, 0.80 mmol), and the mixture was stirred overnight at room temperature. The reaction solution was diluted with water (100 ml) and extracted with ethyl acetate (100 ml×2). The extract was washed successively with 1N hydrochloric acid, 1N aqueous sodium hydroxide solution and saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. Recrystallization of the residue from ethyl acetate-hexane gave the title compound (363 mg, 83%).

후처리

  1. extractionextracted with ethyl acetate (100 ml×2)
  2. washThe extract was washed successively with 1N hydrochloric acid, 1N aqueous sodium hydroxide solution and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customevaporated under reduced pressure
  5. customRecrystallization of the residue from ethyl acetate-hexane

출처 및 근거

ORD 기록
ord-84db0a583057438585a651094387940f
출처 데이터셋
uspto-grants-2006_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06982348B2

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