Hydrochloric Acid → HCID 136355272, compound

HRID 2358256Notes

Reaction equation

HRID 2358256 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:17])[CH2:9][C:10]2[CH:15]=[CH:14][N:13]=[C:12]([F:16])[CH:11]=2)=[CH:4][CH:3]=1.C([O:22][N:23]=O)(C)(C)C.Cl>C(O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8](=[O:17])[C:9]([C:10]2[CH:15]=[CH:14][N:13]=[C:12]([F:16])[CH:11]=2)=[N:23][OH:22])=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 10906Tert-Butyl nitriteHCID 53434041HCID 53434041, compound

Product 1

HCID 136355272HCID 136355272, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
-5 °C

Procedure

To a solution of the intermediate from Example 1 Step A (48 g, 0.163 mol) in ethanol (800 mL) at −10° C. was added dropwise t-butylnitrite (22.1 mL, 0.18 mol) over 10 minutes, followed by 2.5 N HCl in absolute ethanol (52 mL, 0.13 mol). The reaction temperature was maintained at −5° C. during these additions. After the addition was completed, the dry ice bath was removed and the reaction was allowed to warm to RT overnight. The ethanol was removed under reduced pressure and the residue was diluted with H2O. The aqueous phase was made basic with saturated NaHCO3 and extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The crude residue was taken up in methanol/isopropanol and mixed with toluene. The methanol/isopropanol mixture was concentrated under reduced pressure and the title compound was recrystallized from hexane/toluene. 1H NMR (400 MHz, CDCl3): δ8.22 (m, 1H), 7.78 (m, 2H), 7.65 (m, 2H), 7.32 (m, 1H), 7.08(s, 1H).

Workup

  1. additionAfter the addition
  2. customthe dry ice bath was removed
  3. temperatureto warm to RT overnight
  4. customThe ethanol was removed under reduced pressure
  5. additionthe residue was diluted with H2O
  6. extractionextracted with EtOAc
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. additionmixed with toluene
  11. concentrationThe methanol/isopropanol mixture was concentrated under reduced pressure
  12. customthe title compound was recrystallized from hexane/toluene

Sources & evidence

ORD record
ord-f3ef9ac1e6784bd8918072954ae38946
Source dataset
uspto-grants-2010_07
Patent number
US07763634B2

Reaction notes

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