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Hydrogen Bromide → 4-(2-Chloro-4-methylphenylcarbamoyl)-3-{4-cyclopropyl-5-[3-(2-ethylbutyl)cyclobutyl]isoxazol-3-yl}butanoic acid

HRID 1912100
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HRID 1912100 반응식
[Cl:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]([CH2:12][CH:13]([C:22]1[C:26]([CH:27]2[CH2:29][CH2:28]2)=[C:25]([CH:30]2[CH2:33][CH:32]([CH2:34][CH:35]([CH2:38][CH3:39])[CH2:36][CH3:37])[CH2:31]2)[O:24][N:23]=1)[CH2:14][C:15]([O:17]C(C)(C)C)=[O:16])=[O:11].O.Br.[OH-].[Na+]>C(O)(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]([CH2:12][CH:13]([C:22]1[C:26]([CH:27]2[CH2:28][CH2:29]2)=[C:25]([CH:30]2[CH2:31][CH:32]([CH2:34][CH:35]([CH2:38][CH3:39])[CH2:36][CH3:37])[CH2:33]2)[O:24][N:23]=1)[CH2:14][C:15]([OH:17])=[O:16])=[O:11]
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참가 물질

6

반응물 4

HCID 260Hydrogen BromideHCID 962WaterHCID 14798Sodium HydroxideHCID 86675054tert-Butyl 4-(2-chloro-4-methylphenylcarbamoyl)-3-{4-cyclopropyl-5-[3-(2-ethylbutyl)cyclobutyl]isoxazol-3-yl}butanoate

생성물 1

HCID 711146954-(2-Chloro-4-methylphenylcarbamoyl)-3-{4-cyclopropyl-5-[3-(2-ethylbutyl)cyclobutyl]isoxazol-3-yl}butanoic acid수율 51.7%

시약·촉매·용매 1

HCID 176Acetic Acid용매

실험 절차

tert-Butyl 4-(2-chloro-4-methylphenylcarbamoyl)-3-{4-cyclopropyl-5-[3-(2-ethylbutyl)cyclobutyl]isoxazol-3-yl}butanoate (122 mg) and water (0.7 mL) were mixed. To the mixture was added a solution of 25 w/w % hydrogen bromide in acetic acid (1.4 mL) at ice temperature. After stirring at RT for 2 hr, aqueous 4 N sodium hydroxide (1.65 mL) was added to the reaction mixture at ice temperature. The mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, then dried over magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was concentrated in vacuo. The resultant residue was purified by preparative chromatography (Eluent: methanol/chloroform/acetic acid=1/20/0.1) to give the title compound (56.7 mg). The title compound was analyzed using a chiral column. The retention time of the title compound was 8.2 min., and the optical purity thereof was 90.5% ee.

후처리

  1. extractionThe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationThe magnesium sulfate was filtered off
  5. concentrationthe filtrate was concentrated in vacuo
  6. customThe resultant residue was purified by preparative chromatography (Eluent: methanol/chloroform/acetic acid=1/20/0.1)

출처 및 근거

ORD 기록
ord-9d56445878a94f99b33c7bdb553e50d8
출처 데이터셋
uspto-grants-2013_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08604069B2

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