N,N-Dimethylglycine → HCID 57864747, compound

HRID 2425534Notes

Reaction equation

HRID 2425534 reaction equation
[CH3:1][O:2][C:3]1[CH:29]=[C:28]([O:30][CH3:31])[CH:27]=[CH:26][C:4]=1[CH2:5][N:6]1[CH2:10][C@@H:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2Br)[C@H:8]([C:18]2[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:19]=2[OH:25])[CH2:7]1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)CC(O)=O.C1(C)C=CC=CC=1>O1CCOCC1.[Cu]I>[Cl:24][C:22]1[CH:21]=[CH:20][C:19]2[O:25][C:16]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[C@H:9]3[CH2:10][N:6]([CH2:5][C:4]4[CH:26]=[CH:27][C:28]([O:30][CH3:31])=[CH:29][C:3]=4[O:2][CH3:1])[CH2:7][C@@H:8]3[C:18]=2[CH:23]=1

Participants

7

Reactant 4

HCID 673N,N-DimethylglycineHCID 1140TolueneHCID 10796Cesium carbonateHCID 67245677HCID 67245677, compound

Product 1

HCID 57864747HCID 57864747, compoundYield 108.5%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of racemic trans-2-(1-(2,4-dimethoxybenzyl)-4-(2-bromophenyl)pyrrolidin-3-yl)-4-chlorophenol (6.8 g, 13.54 mmol), cesium carbonate (8.83 g, 27.1 mmol, 2.0 eq.), N,N-dimethylglycine (558 mg, 5.42 mmol; 0.4 eq.) and CuI (1.03 g, 5.42 mmol; 0.4 eq.) in dioxane (75 ml) was heated to reflux temperature overnight while stirring under inert nitrogen atmosphere to give 90% conversion according to LC-MS (M+1=422, 424 found). The reaction mixture was cooled to room temperature and was then filtered over a glass filter. The residual salts were washed with dioxane (25 ml). The combined filtrates were concentrated under vacuum to give the crude product as a brown oil. Toluene (150 ml) was added and the resulting solution was washed with concentrated aqueous ammonia (25 ml; 25%). The toluene layer was separated and dried with Na2SO4. Concentration under vacuum gave crude trans-5-chloro-2,3,3a,12b-tetrahydro-2-(2,4-dimethoxybenzyl)-1H-dibenz[2,3:6,7]-oxepino[4,5-c]pyrrole (6.2 g) in quantitative yield as a brown oil, with ca. 70% purity according to LC-MS analysis. The product was used without further purification.

Workup

  1. temperaturewas heated
  2. temperatureto reflux temperature overnight
  3. customto give 90% conversion
  4. filtrationwas then filtered over a glass
  5. filtrationfilter
  6. washThe residual salts were washed with dioxane (25 ml)
  7. concentrationThe combined filtrates were concentrated under vacuum
  8. customto give the crude product as a brown oil
  9. washthe resulting solution was washed with concentrated aqueous ammonia (25 ml; 25%)
  10. customThe toluene layer was separated
  11. dry with materialdried with Na2SO4
  12. concentrationConcentration under vacuum

Sources & evidence

ORD record
ord-a9dd790fdf6542418368c2bc9f8accc6
Source dataset
uspto-grants-2011_06
Patent number
US07964739B2

Reaction notes

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