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Acetic Acid → {1-Dimethylcarbamoyl-2-[4-(5-hydroxycarbamoyl-pyridin-2-yloxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester

HRID 273440
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HRID 273440 반응식
[C:1]([O:5][C:6]([NH:8][CH:9]([C:27](=[O:31])[N:28]([CH3:30])[CH3:29])[CH2:10][C:11]1[CH:26]=[CH:25][C:14]([O:15][C:16]2[CH:24]=[CH:23][C:19]([C:20]([OH:22])=O)=[CH:18][N:17]=2)=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.Cl.[NH2:40][OH:41].C(O)(=O)C>CN(C=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]([C:27](=[O:31])[N:28]([CH3:29])[CH3:30])[CH2:10][C:11]1[CH:26]=[CH:25][C:14]([O:15][C:16]2[CH:24]=[CH:23][C:19]([C:20](=[O:22])[NH:40][OH:41])=[CH:18][N:17]=2)=[CH:13][CH:12]=1)([CH3:4])([CH3:2])[CH3:3]
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참가 물질

6

반응물 4

HCID 176Acetic AcidHCID 79724-MethylmorpholineHCID 443297Hydroxyamine hydrochlorideHCID 691138456-[4-(2-Tert-butoxycarbonylamino-2-dimethylcarbamoyl-ethyl)-phenoxy]-nicotinic acid

생성물 1

HCID 72575122{1-Dimethylcarbamoyl-2-[4-(5-hydroxycarbamoyl-pyridin-2-yloxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester수율 98%

시약·촉매·용매

1
HCID 6228Dimethylformamide용매

실험 절차

The acid compound 19 (1.0 g, 2.328 mmol) was dissolved in dry DMF and stirred under an atmosphere of argon. N-Methylmorpholine (1.02 mL, 9.32 mmol) was added. After 20 min, hydroxylamine hydrochloride (0.323 g, 4.66 mmol) was added and the reaction mixture was warmed up to room temperature and stirred overnight. The solvent was removed under reduced pressure and residual material was partitioned between EtOAc (50 mL) and saturated NH4Cl solution (1×30 mL). The organic layer was dried and concentrated to yield the crude material. Flash chromatography on SiO2 gel using hexanes-ethyl acetate (70-60%) mixture containing 1% acetic acid furnished the desired hydroxamic acid compound 20 (0.5 g, 98%) 1H NMR (400 MHz, DMSO-d6): 8.47 (br, 1H) 8.14 (dd, J=8.8 and 2.4 Hz, 1H), 7.29 (d, J=8.4 Hz, 2H), 7.11 (d, J=8.8 Hz, 1H), 7.05 (m, 3H), 4.56 (m, 1H), 2.93 (s, 3H) 2.85-2.75 (m, 2H), 2.79 (s, 3H), 1.32 (s, 9H)

후처리

  1. stirringstirred overnight
  2. customThe solvent was removed under reduced pressure and residual material
  3. customwas partitioned between EtOAc (50 mL) and saturated NH4Cl solution (1×30 mL)
  4. customThe organic layer was dried
  5. concentrationconcentrated
  6. customto yield the crude material

출처 및 근거

ORD 기록
ord-ee5a02531ee045ab9dbffc53d7c2aed7
출처 데이터셋
uspto-grants-2008_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07456292B2

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