N,N'-Dimethylethylenediamine → {(3S)-1-[4-(methoxymethyl)-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl]-5-oxopyrrolidin-3-yl}carbamic acid tert-butyl ester

HRID 1847033노트

반응식

HRID 1847033 반응식
[C:1]([O:5][C:6](=[O:14])[NH:7][C@@H:8]1[CH2:12][C:11](=[O:13])[NH:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].Br[C:16]1[CH:17]=[CH:18][C:19]2[O:24][CH2:23][C:22](=[O:25])[N:21]([CH2:26][O:27][CH3:28])[C:20]=2[CH:29]=1.C(=O)([O-])[O-].[K+].[K+].CNCCNC>[Cu]I.ClCCl.C1(C)C=CC=CC=1>[C:1]([O:5][C:6](=[O:14])[NH:7][C@H:8]1[CH2:12][C:11](=[O:13])[N:10]([C:16]2[CH:17]=[CH:18][C:19]3[O:24][CH2:23][C:22](=[O:25])[N:21]([CH2:26][O:27][CH3:28])[C:20]=3[CH:29]=2)[CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

참가 물질

8

반응물 4

HCID 8070N,N'-DimethylethylenediamineHCID 11430Potassium CarbonateHCID 71301758(R)-tert-Butyl (5-oxopyrrolidin-3-yl)carbamateHCID 867249556-Bromo-4-(methoxymethyl)-2H-1,4-benzoxazin-3(4H)-one

생성물 1

HCID 86724960{(3S)-1-[4-(methoxymethyl)-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl]-5-oxopyrrolidin-3-yl}carbamic acid tert-butyl ester수율 61.1%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 1140Toluene용매HCID 6344Dichloromethane용매

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온도
100 °C

실험 절차

A mixture of [(3R)-5-oxopyrrolidin-3-yl]carbamic acid tert-butyl ester (synthesized with reference to WO2004/22536; 1.5 g, 7.49 mmol), 6-bromo-4-(methoxymethyl)-2H-1,4-benzoxazin-3(4H)-one (Reference Examples 36; 2.04 g 7.49 mmol), potassium carbonate (3.11 g, 22.5 mmol), copper (I) iodide (1.43 g, 7.49 mmol), N,N′-dimethylethylenediamine (0.80 ml, 7.49 mmol) and toluene (95 ml) was stirred overnight at 100° C. under a stream of nitrogen gas. After cooling, dichloromethane was added to the reaction solution to remove insoluble material by filtration and the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate) to yield 1.79 g (61%) of the title compound in the form of a colorless foamy solid.

후처리

  1. temperatureAfter cooling
  2. customto remove insoluble material
  3. filtrationby filtration
  4. customthe solvent was removed under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate)

출처 및 근거

ORD 기록
ord-4822c646788a403fa467b2439fc31df0
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08952010B2

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