Acetic Anhydride → HCID 178432476, compound

HRID 1524881Notes

Reaction equation

HRID 1524881 reaction equation
[C:1]([O:5][C:6](=[O:29])[NH:7][C@H:8]([C:16]1[NH:17][CH:18]=[C:19]([C:21]2[CH:26]=[CH:25][C:24]([C:27]#[N:28])=[CH:23][CH:22]=2)[N:20]=1)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].Cl.NO.[CH2:33]([N:35](CC)CC)[CH3:34].C(OC(=O)C)(=[O:42])C>CCO>[C:1]([O:5][C:6](=[O:29])[NH:7][C@H:8]([C:16]1[NH:17][CH:18]=[C:19]([C:21]2[CH:22]=[CH:23][C:24]([C:27]3[N:35]=[C:33]([CH3:34])[O:42][N:28]=3)=[CH:25][CH:26]=2)[N:20]=1)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 443297Hydroxyamine hydrochlorideHCID 178454144HCID 178454144, compound

Product 1

HCID 178432476HCID 178432476, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

{(S)-1-[4-(4-Cyanophenyl)-1H-imidazol-2-yl]-2-phenylethyl}carbamic acid tert-butyl ester prepared as described in Example 28 Part A (1.00 equiv; 2.57 mmoles; 1.00 g) was dissolved in 15 mL EtOH and Hydroxylamine Hydrochloride (12.87 mmoles; 894.42 mg) and Triethylamine (12.87 mmoles; 1.79 mL) were added. The resulting solution was heated at reflux in an 80° C. oil bath under N2 overnight. Reaction was cooled to room temperature and evaporated to remove EtOH. Residue was suspended in a mixture of EtOAc/EtOH (˜10:1) and filtered to remove inorganic solids. Filtrate was reconcentrated to a yellow foam. This residue was redissolved in 10 mL HOAc and treated with stirring under N2 with Acetic Anhydride (4.23 mmoles; 400 μL). Solution was stirred for 20 min at room temperature, then heated in 80° C. oil bath for 2 h, cooled to room temperature and stirred overnight. Most of HOAc was removed on rotary evaporator, then residue was diluted with water and carefully neutralized by addition of sat'd NaHCO3 to pH˜8. Extracted 3× with CH2Cl2. Combined extracts were washed with brine then dried over MgSO4, filtered and evaporated to a lt red foam. Residue was purified on silica gel to provide the product as a lt pinkish tan foam. (590 mg; 51.4%). 1H NMR (500 MHz, CDCl3) δ 1.41 (s, 9H) 2.65 (s, 3H) 3.28-3.44 (m, 2H) 4.88 (d, J=7.70 Hz, 1H) 5.23 (s, 1H) 7.13-7.36 (m, 5H) 7.42-7.55 (m, 1H) 7.88 (d, J=8.25 Hz, 2H) 8.06 (d, J=8.25 Hz, 2H) 9.67 (s, 1H). m/z 446.1 (M+H)+.

Workup

  1. temperatureThe resulting solution was heated
  2. customReaction
  3. temperaturewas cooled to room temperature
  4. customevaporated
  5. customto remove EtOH
  6. additionResidue was suspended in a mixture of EtOAc/EtOH (˜10:1)
  7. filtrationfiltered
  8. customto remove inorganic solids
  9. dissolutionThis residue was redissolved in 10 mL HOAc
  10. additiontreated
  11. temperatureheated in 80° C. oil bath for 2 h
  12. temperaturecooled to room temperature
  13. stirringstirred overnight
  14. customMost of HOAc was removed on rotary evaporator
  15. additionresidue was diluted with water
  16. additioncarefully neutralized by addition of sat'd NaHCO3 to pH˜8
  17. extractionExtracted 3× with CH2Cl2
  18. washCombined extracts were washed with brine
  19. dry with materialthen dried over MgSO4
  20. filtrationfiltered
  21. customevaporated to a lt red foam
  22. customResidue was purified on silica gel

Sources & evidence

ORD record
ord-d1d8a5e3fdea49a4b4d5f62465b146b2
Source dataset
uspto-grants-2015_07
Patent number
US09079860B2

Reaction notes

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