N,N,N',N'-Tetramethylethylenediamine → 2,2-Dimethyl-5-{3-[(5-methyl-2-phenyloxazol-4-yl)methyl]benzyl}-1,3-dioxane

HRID 1796365Notes

Reaction equation

HRID 1796365 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=1)[CH2:5][CH:6]1[CH2:11][O:10][C:9]([CH3:13])([CH3:12])[O:8][CH2:7]1.C(=O)=O.CC(C)=O.CN(C)CCN(C)C.C([Li])CCC.C(P(CCCC)CCCC)CCC.I[CH2:51][C:52]1[N:53]=[C:54]([C:58]2[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=2)[O:55][C:56]=1[CH3:57]>O1CCCC1.[Cu](I)I>[CH3:12][C:9]1([CH3:13])[O:10][CH2:11][CH:6]([CH2:5][C:4]2[CH:14]=[CH:15][CH:16]=[C:2]([CH2:51][C:52]3[N:53]=[C:54]([C:58]4[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=4)[O:55][C:56]=3[CH3:57])[CH:3]=2)[CH2:7][O:8]1

Participants

9

Reactant 6

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 13831TributylphosphineHCID 18522661Acetone cardiceHCID 218667465-(3-Bromobenzyl)-2,2-dimethyl-1,3-dioxaneHCID 224936584-(Iodomethyl)-5-methyl-2-phenyl-1,3-oxazoleHCID 178418339Butyllithium

Product 1

HCID 218667752,2-Dimethyl-5-{3-[(5-methyl-2-phenyloxazol-4-yl)methyl]benzyl}-1,3-dioxaneYield 17.7%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

Under argon flow, 1.45 g of 5-(3-bromobenzyl)-2,2-dimethyl-1,3-dioxane was dissolved in 7 ml of dry tetrahydrofuran, and cooled with the dry ice-acetone bath. To the mixture was added 0.9 ml of N,N,N′,N′-tetramethylethylenediamine, and then n-butyllithium (1.6 M hexane solution) was added dropwise at −60° C. or less. After 10-minute-stirring, a suspension of 1.03 g of tri-n-butylphosphine and 0.97 g of copper iodide/7 ml of dry tetrahydrofuran was added and the mixture was stirred for 10 minutes. A solution of 1.52 g of 4-iodomethyl-5-methyl-2-phenyloxazole/7 ml of dry tetrahydrofuran was added dropwise at −60° C. or less, and the mixture was stirred for 15 minutes under the same conditions. The bath was removed and the mixture was stirred for 1.5 hours. To the reaction solution was added saturated aqueous ammonium chloride solution. The mixture was diluted with water, extracted with ether, filtrated to remove insolubles, washed with water, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (Wakogel® C-200, n-hexane:ethyl acetate=4:1) to provide 0.34 g of the objective compound as white crystals. M.p. 85–87° C.

Workup

  1. additionwas added
  2. stirringthe mixture was stirred for 10 minutes
  3. stirringthe mixture was stirred for 15 minutes under the same conditions
  4. customThe bath was removed
  5. stirringthe mixture was stirred for 1.5 hours
  6. additionTo the reaction solution was added saturated aqueous ammonium chloride solution
  7. additionThe mixture was diluted with water
  8. extractionextracted with ether
  9. filtrationfiltrated
  10. customto remove insolubles
  11. washwashed with water
  12. dry with materialdried over anhydrous magnesium sulfate
  13. concentrationconcentrated
  14. customThe residue was purified by silica gel column chromatography (Wakogel® C-200, n-hexane:ethyl acetate=4:1)

Sources & evidence

ORD record
ord-d5c48f2647f74e8da4bdb7c746aa6a6f
Source dataset
uspto-grants-2006_04
Patent number
US07030143B2

Reaction notes

Loading…