Diphosgene → HCID 178450552, compound

HRID 227152Notes

Reaction equation

HRID 227152 reaction equation
[O:1]=[C:2](Cl)OC(Cl)(Cl)Cl.C1(C)C=CC=CC=1.O1CCCC1.[NH2:21][C@H:22]([C:44]1[CH:49]=[CH:48][C:47]([O:50][CH2:51][CH2:52][O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[CH:46][CH:45]=1)[C:23]([NH:25][C@H:26]([C:34]1[NH:38][C:37]2[CH:39]=[CH:40][C:41]([I:43])=[CH:42][C:36]=2[N:35]=1)[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:24].C(N(CC)C(C)C)(C)C>O1CCCC1>[C:54]([O:53][CH2:52][CH2:51][O:50][C:47]1[CH:46]=[CH:45][C:44]([C@H:22]2[NH:21][C:2](=[O:1])[N:25]([C@H:26]([C:34]3[NH:38][C:37]4[CH:39]=[CH:40][C:41]([I:43])=[CH:42][C:36]=4[N:35]=3)[CH2:27][C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[C:23]2=[O:24])=[CH:49][CH:48]=1)([CH3:57])([CH3:56])[CH3:55]

Participants

6

Reactant 4

HCID 10426DiphosgeneHCID 81531DiisopropylethylamineHCID 22635083Tetrahydrofuran tolueneHCID 178450553HCID 178450553, compound

Product 1

HCID 178450552HCID 178450552, compoundYield 91.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of diphosgene (29 μL, 0.24 mmol) in 1:1 v/v toluene/tetrahydrofuran (20 mL) at −78° C. under an atmosphere of nitrogen was added a solution of (R)-2-amino-2-[4-(2-tert-butoxy-ethoxy)-phenyl]-N-[(S)-1-(5-iodo-1H-benzoimidazol-2-yl)-2-phenyl-ethyl]-acetamide (210 mg, 0.34 mmol) and N,N-diisopropylethylamine (239 μL, 1.37 mmol) in tetrahydrofuran (6 mL) dropwise with stirring. The reaction was allowed to warm to −20° C. then quenched with ice water (10 mL) and stirred for 10 minutes. The mixture was poured into ethyl acetate (30 mL) and the layers were separated. The aqueous layer was extracted with ethyl acetate (20 mL) and the organic extracts were combined, washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by chromatography over silica gel gradient eluted with 20 to 60% v/v ethyl acetate/hexanes to give (R)-5-[4-(2-tert-butoxy-ethoxy)-phenyl]-3-[(S)-1-(5-iodo-1H-benzoimidazol-2-yl)-2-phenyl-ethyl]-imidazolidine-2,4-dione (140 mg, 64%).

Workup

  1. customthen quenched with ice water (10 mL)
  2. stirringstirred for 10 minutes
  3. additionThe mixture was poured into ethyl acetate (30 mL)
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted with ethyl acetate (20 mL)
  6. washwashed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by chromatography over silica gel gradient
  11. washeluted with 20 to 60% v/v ethyl acetate/hexanes

Sources & evidence

ORD record
ord-ad7417120ac54fbf93e1b4d4d864e70d
Source dataset
uspto-grants-2009_07
Patent number
US07557221B2

Reaction notes

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