Iodine → HCID 90456722, 화합물

HRID 625872노트

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HRID 625872 반응식
II.[C:3]([O:7][C:8]([NH:10][C@@H:11]([CH2:16]I)[C:12]([O:14][CH3:15])=[O:13])=[O:9])([CH3:6])([CH3:5])[CH3:4].C1(P(C2CCCCC2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:31]2[C:36](OC)=[CH:35][CH:34]=[CH:33][C:32]=2OC)CCCCC1.Br[C:48]1[CH:49]=[C:50]([Cl:56])[C:51]([F:55])=[C:52]([Cl:54])[CH:53]=1>CCOC(C)=O.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CN(C=O)C>[CH:33]1[C:32]2[CH:6]([CH2:3][O:7][C:8]([NH:10][C@@H:11]([CH2:16][C:48]3[CH:53]=[C:52]([Cl:54])[C:51]([F:55])=[C:50]([Cl:56])[CH:49]=3)[C:12]([OH:14])=[O:13])=[O:9])[C:25]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:31]=2[CH:36]=[CH:35][CH:34]=1.[C:3]([O:7][C:8]([NH:10][C@@H:11]([CH2:16][C:48]1[CH:53]=[C:52]([Cl:54])[C:51]([F:55])=[C:50]([Cl:56])[CH:49]=1)[C:12]([O:14][CH3:15])=[O:13])=[O:9])([CH3:6])([CH3:5])[CH3:4]

참가 물질

10

반응물 4

HCID 807Iodine2회HCID 10903591methyl (2R)-2-(((tert-butoxy)carbonyl)amino)-3-iodopropanoateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 229262305-Bromo-1,3-dichloro-2-fluorobenzene

생성물 2

HCID 90456722HCID 90456722, 화합물HCID 90456910HCID 90456910, 화합물

시약·촉매·용매 4

HCID 23994Zinc촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To an oven dried 8 mL vial with teflon cap purged with N2 was added Zinc dust (298 mg, 4.56 mmol), DMF (1.5 mL), and iodine (57.8 mg, 0.228 mmol). To this mixture was added (R)-methyl 2-((tert-butoxycarbonyl)amino)-3-iodopropanoate (500 mg, 1.519 mmol), immediately followed by iodine (57.8 mg, 0.228 mmol). Pd2(dba)3 (69.6 mg, 0.076 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (62.4 mg, 0.152 mmol), 5-bromo-1,3-dichloro-2-fluorobenzene (556 mg, 2.279 mmol) and the reaction mixture was allowed to stir at rt for 16 h. The crude mixture was diluted in 30 mL of EtOAc and DMF was removed using four aqueous washes. The organic phase was dried over anhydrous sodium sulfate. The solution was filtered and concentrated and the crude product was purified by silica gel chromatography using 100% hexanes to 30% EtOAc/Hexanes. The desired product was obtained as a pale yellow oil, (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(3,5-dichloro-4-fluorophenyl)propanoate, 0.102 g which was taken into next step directly.

후처리

  1. dry with materialTo an oven dried 8 mL vial with teflon
  2. customcap
  3. custompurged with N2
  4. customDMF was removed
  5. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  6. filtrationThe solution was filtered
  7. concentrationconcentrated
  8. customthe crude product was purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-564cd7e2d0624118a904646381e4cfdd
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09308236B2

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