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

HRID 1847028Notes

Reaction equation

HRID 1847028 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 86724956{(3R)-1-[4-(Methoxymethyl)-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl]-5-oxopyrrolidin-3-yl}carbamic acid tert-butyl esterYield 96%

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; 200 mg, 0.999 mmol), 6-bromo-4-(methoxymethyl)-2H-1,4-benzoxazin-3(4H)-one (272 mg, 0.999 mmol), potassium carbonate (415 mg, 3.0 mmol), copper (I) iodide (190 mg, 0.999 mmol), N,N′-dimethylethylenediamine (0.107 ml, 0.999 mmol) and toluene (4 ml) was stirred overnight at 100° C. under a stream of nitrogen gas. After cooling, dichloromethane was added to the reaction solution and insoluble material was removed by filtration. The solvent of the filtrate was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate) to yield 375 mg (96%) of the title compound in the form of a colorless foamy solid.

Workup

  1. temperatureAfter cooling
  2. customwas removed by filtration
  3. customThe solvent of the filtrate was removed under reduced pressure
  4. customThe obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-e2d7f9996c74487192ecfa9f04d54dad
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

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