N,N'-Dimethylethylenediamine → tert-Butyl [(3R)-1-{4-[(Benzyloxy)methyl]-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl}-5-oxopyrrolidin-3-yl]carbamate

HRID 1847076Notes

Reaction equation

HRID 1847076 reaction equation
[CH2:1]([O:8][CH2:9][N:10]1[C:15]2[CH:16]=[C:17](Br)[CH:18]=[CH:19][C:14]=2[O:13][CH2:12][C:11]1=[O:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:22]=[C:23]1[NH:27][CH2:26][C@H:25]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:24]1.C(=O)([O-])[O-].[Cs+].[Cs+].CNCCNC>C(Cl)(Cl)Cl.CO.[Cu]I.O1CCOCC1>[CH2:1]([O:8][CH2:9][N:10]1[C:15]2[CH:16]=[C:17]([N:27]3[C:23](=[O:22])[CH2:24][C@@H:25]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:33])([CH3:32])[CH3:34])[CH2:26]3)[CH:18]=[CH:19][C:14]=2[O:13][CH2:12][C:11]1=[O:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 10796Cesium carbonateHCID 71301758tert-Butyl [(3R)-5-oxopyrrolidin-3-yl]carbamateHCID 867249994-[(Benzyloxy)methyl]-6-bromo-2H-1,4-benzoxazin-3(4H)-one

Product 1

HCID 86725000tert-Butyl [(3R)-1-{4-[(Benzyloxy)methyl]-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl}-5-oxopyrrolidin-3-yl]carbamateYield 80%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolventHCID 21584188Chloroform methanolSolvent

Conditions

Temperature
100 °C

Procedure

In a reaction vessel were weighed and charged 4-[(Benzyloxy)methyl]-6-bromo-2H-1,4-benzoxazin-3(4H)-one (366 mg, 1.05 mmol), tert-butyl [(3R)-5-oxopyrrolidin-3-yl]carbamate (200 mg, 1.00 mmol), cesium carbonate (652 mg, 2.00 mmol) and 1,4-dioxane (5 ml), which was purged with nitrogen gas, subsequently copper (I) iodide (190 mg, 1.00 mmol) and N,N′-dimethylethylenediamine (0.107 ml, 1.00 mmol) were added thereto, and the mixture was stirred with heating for 9 hours on an oil bath at 100° C. After lowering the temperature to room temperature, the reaction solution was diluted with a mixed solvent of chloroform-methanol (9:1) to remove insoluble material by filtration using celite. The filtrate was concentrated under reduced pressure. The residue was roughly purified by silica gel column chromatography (chloroform/methanol), subsequently crystallized in a mixed solvent of n-hexane-ethyl acetate (1:1) and collected by filtration to yield 373 mg (80%) of the title compound in the form of a white solid.

Workup

  1. customIn a reaction vessel were weighed
  2. additionwere added
  3. customto room temperature
  4. customto remove insoluble material
  5. filtrationby filtration
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customThe residue was roughly purified by silica gel column chromatography (chloroform/methanol)
  8. customsubsequently crystallized in a mixed solvent of n-hexane-ethyl acetate (1:1)
  9. filtrationcollected by filtration

Sources & evidence

ORD record
ord-e7427d7758ea42f7b1ccd3bf95aa81ef
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

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