4-Methyloxybenzyl chloride → Tert-butyl (3-bromo-2-chloro-5-(difluoromethyl)phenyl)(4-methoxybenzyl)carbamate

HRID 1430790노트

반응식

HRID 1430790 반응식
[Br:1][C:2]1[C:3]([Cl:19])=[C:4]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH:5]=[C:6]([CH:8]([F:10])[F:9])[CH:7]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH3:30][O:31][C:32]1[CH:39]=[CH:38][C:35]([CH2:36]Cl)=[CH:34][CH:33]=1.[Li+].[Cl-]>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[C:3]([Cl:19])=[C:4]([N:11]([CH2:36][C:35]2[CH:38]=[CH:39][C:32]([O:31][CH3:30])=[CH:33][CH:34]=2)[C:12](=[O:18])[O:13][C:14]([CH3:15])([CH3:16])[CH3:17])[CH:5]=[C:6]([CH:8]([F:10])[F:9])[CH:7]=1

참가 물질

7

반응물 4

HCID 699934-Methyloxybenzyl chlorideHCID 433294Lithium ChlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 86708469tert-Butyl (3-bromo-2-chloro-5-(difluoromethyl)phenyl)carbamate

생성물 1

HCID 86708468Tert-butyl (3-bromo-2-chloro-5-(difluoromethyl)phenyl)(4-methoxybenzyl)carbamate수율 94.2%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

tert-Butyl (3-bromo-2-chloro-5-(difluoromethyl)phenyl)carbamate (1.82 g, 5.10 mmol) was dissolved in DMF (11.1 mL) at room temperature. NaHMDS (6.12 mL, 6.12 mmol) was added dropwise and the reaction was stirred for 30 minutes before the addition of 4-methoxybenzyl chloride (0.904 mL, 6.64 mmol) and stirring overnight. The reaction mixture was diluted with EtOAc causing a ppt to form. 10% aq. LiCl solution was added and the two layers became clear with stirring. The mixture was poured into a separatory funnel and the organic layer was washed with an extra equivalent of 10% aq. LiCl solution. The organic layer was dried over Na2SO4 and concentrated. Column chromatography (220 g SiO2, 0 to 8% EtOAc-hexane, gradient elution) afforded the expected product tert-butyl (3-bromo-2-chloro-5-(difluoromethyl)phenyl)(4-methoxybenzyl)carbamate (2.29 g).

후처리

  1. customto form
  2. stirringwith stirring
  3. additionThe mixture was poured into a separatory funnel
  4. washthe organic layer was washed with an extra equivalent of 10% aq. LiCl solution
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated
  7. washColumn chromatography (220 g SiO2, 0 to 8% EtOAc-hexane, gradient elution)

출처 및 근거

ORD 기록
ord-0ac17ecd529646b5b1c22e93c3933171
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940736B2

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