Triphenylphosphine Oxide → (5R)-5-[(4-bromophenyl)methyl]-7-(3,5-dichlorophenyl)-5-methyl-2H-imidazo[1,2-a]imidazole-3,6-dione

HRID 2303982Notes

Reaction equation

HRID 2303982 reaction equation
C([O:3][C:4](=O)[CH2:5][N:6]=[C:7]1[NH:11][C@@:10]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([Br:20])=[CH:16][CH:15]=2)([CH3:12])[C:9](=[O:21])[N:8]1[C:22]1[CH:27]=[C:26]([Cl:28])[CH:25]=[C:24]([Cl:29])[CH:23]=1)C.C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C[Al](C)C>C1(C)C=CC=CC=1>[Br:20][C:17]1[CH:16]=[CH:15][C:14]([CH2:13][C@@:10]2([CH3:12])[N:11]3[C:4](=[O:3])[CH2:5][N:6]=[C:7]3[N:8]([C:22]3[CH:23]=[C:24]([Cl:29])[CH:25]=[C:26]([Cl:28])[CH:27]=3)[C:9]2=[O:21])=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 13097Triphenylphosphine OxideHCID 16682925Trimethylaluminum2×HCID 135421360HCID 135421360, compound

Product 1

HCID 11190535(5R)-5-[(4-bromophenyl)methyl]-7-(3,5-dichlorophenyl)-5-methyl-2H-imidazo[1,2-a]imidazole-3,6-dioneYield 89%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Conditions

Temperature
-10 °C

Procedure

Toluene (450 mL) was added to 76.9 g of a mixture of the product of Example 2(47.1 g, 91.7 mmol) and triphenylphosphine oxide (29.2 g, 105 mmol), and the resulting solution was cooled down to −10° C. Trimethylaluminum (46 mL of a 2 M solution in toluene, 92 mmol) was added dropwise keeping the temperature at or below 0° C. and the mixture was then allowed to reach ambient temperature. The mixture was stirred at ambient temperature for two h and more trimethylaluminum (27.6 mL of a 2 M solution in toluene, 55.2 mmol) was added in two portions at two h intervals. The mixture was placed over an ice bath and slowly quenched with 1 N HCl (360 mL). The organic portion was separated and the aqueous portion was extracted with toluene (200 mL). The combined organic portions were washed with water and concentrated under reduced pressure to afford an orange oil. Flash chromatography (silica gel, hexane/ethyl acetete 4:1 v/v) afforded 38.1 g (89%) of product as an oil that solidified upon standing: mp 52-54° C.; 1H NMR (400 MHz, CDCl3) δ 1.84 (s, 3H), 3.24(d, J=13.8 Hz, 1H), 3.43 (d, J=13.8 Hz, 1H), 4.18 (d, J=21.9 Hz, 1H), 4.30 (d, J=21.9 Hz, 1H), 6.95(d, J=8.3 Hz, 2H), 7.29 (d, J=1.8 Hz 2H), 7.33 (t, J=1.8 Hz, 1H), 7.38 (d, J=8.3 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 21.5, 40.8, 61.3, 65.1, 122.3, 122.6, 128.5, 131.0, 132.0, 132.5, 132.7, 135.5, 154.6, 174.3, 174.9; Anal. calcd for C19H14BrC12N3O2: C, 48.85; H, 3.02; N, 9.00. Found C, 48.89; H, 3.02; N, 8.81.

Workup

  1. custombelow 0° C.
  2. customto reach ambient temperature
  3. additionwas added in two portions at two h intervals
  4. customThe mixture was placed over an ice bath
  5. customslowly quenched with 1 N HCl (360 mL)
  6. customThe organic portion was separated
  7. extractionthe aqueous portion was extracted with toluene (200 mL)
  8. washThe combined organic portions were washed with water
  9. concentrationconcentrated under reduced pressure
  10. customto afford an orange oil

Sources & evidence

ORD record
ord-9728400778c04785b59810f177d71f5e
Source dataset
uspto-grants-2002_08
Patent number
US06433183B1

Reaction notes

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