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 1847033Notes

Reaction equation

HRID 1847033 reaction equation
[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]

Participants

8

Reactant 4

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

Product 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 esterYield 61.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-4822c646788a403fa467b2439fc31df0
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

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