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Citric Acid → Acetic acid 2-hydroxycarbamoyl-1-(4-methoxy-benzenesulfonyl)-2,3,4,7-tetrahydro-1H-azepin-3-ylmethyl ester

HRID 1872247
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HRID 1872247 반응식
[C:1]([O:4][CH2:5][CH:6]1[CH2:12][CH:11]=[CH:10][CH2:9][N:8]([S:13]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)(=[O:15])=[O:14])[CH:7]1[C:24]([OH:26])=O)(=[O:3])[CH3:2].C([Si](C)(C)[O:32][NH2:33])(C)(C)C.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C=O.C(OCC)(=O)C>[OH:32][NH:33][C:24]([CH:7]1[CH:6]([CH2:5][O:4][C:1](=[O:3])[CH3:2])[CH2:12][CH:11]=[CH:10][CH2:9][N:8]1[S:13]([C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=1)(=[O:15])=[O:14])=[O:26]
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참가 물질

8

반응물 5

HCID 311Citric AcidHCID 81531DiisopropylethylamineHCID 4691350O-(tert-Butyldimethylsilyl)hydroxylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 186896583-Acetoxymethyl-1-(4-methoxy-benzenesulfonyl)-2,3,4,7-tetrahydro-1H-azepine-2-carboxylic acid

생성물 1

HCID 53873648
Acetic acid 2-hydroxycarbamoyl-1-(4-methoxy-benzenesulfonyl)-2,3,4,7-tetrahydro-1H-azepin-3-ylmethyl ester
수율 31.4%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 3-Acetoxymethyl-1-(4-methoxy-benzenesulfonyl)-2,3,4,7-tetrahydro-1H-azepine-2-carboxylic acid (101 mg, 0.263 mmoL) in 3 mL dimethylformamide at -20° C. under an argon blanket was added O-(tert-Butyldimethyl-silyl)hydroxylamine (50 mg, 0.342 mmoL) followed by N,N-Diisopropylethylamine (0.069 mL, 0.342 mmoL). (O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate) (110 mg, 0.289 mmoL) was added in and the temperature was kept at -20° C. for 40 minutes before allowing to warm to ambient temperature. The reaction was allowed to stir for 19 hours at which time it was diluted with ethyl acetate. 10% citric acid was added in and stirred for 30 minutes, the reaction was then washed sequentially with water, 0.5N HCL, dilute sodium bibarbonate, and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, and the solvent removed under reduced pressure. The residue was purified by column chromatography (silica: 0.5% to 3% methanol in dichloromethane) to yield (33 mg, 31%) of Acetic acid 2-hydroxycarbamoyl-1-(4-methoxy-benzenesulfonyl)-2,3,4,7-tetrahydro-1H-azepin-3-ylmethyl ester; MS: (M+H)+ =399, (M+NH4)+ =416.

후처리

  1. stirringstirred for 30 minutes
  2. washthe reaction was then washed sequentially with water, 0.5N HCL, dilute sodium bibarbonate, and brine
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customthe solvent removed under reduced pressure
  6. customThe residue was purified by column chromatography (silica: 0.5% to 3% methanol in dichloromethane)

출처 및 근거

ORD 기록
ord-405519a5347942819f413d227c33f7c1
출처 데이터셋
uspto-grants-2000_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06107291

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