Iodine → HCID 90456722、化合物

HRID 625872ノート

反応式

HRID 625872 の反応式
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]

参加物

10

反応物 4

HCID 807Iodine2 回HCID 10903591methyl (2R)-2-(((tert-butoxy)carbonyl)amino)-3-iodopropanoateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 229262305-Bromo-1,3-dichloro-2-fluorobenzene

生成物 2

HCID 90456722HCID 90456722、化合物HCID 90456910HCID 90456910、化合物

試薬・触媒・溶媒 4

HCID 23994Zinc触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-564cd7e2d0624118a904646381e4cfdd
出典データセット
uspto-grants-2016_04
特許番号
US09308236B2

反応ノート

読み込み中…