Hydrogen Bromide → HCID 68916741, compound

HRID 870368Notes

Reaction equation

HRID 870368 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]2[O:13][CH2:12][CH:11]([NH:14][C:15](=[O:24])OCC3C=CC=CC=3)[CH2:10][C:7]2=[N:8][CH:9]=1)([O-:3])=[O:2].[N+]([C:28]1C=C2C(NC(=O)OCC3C=CC=CC=3)COCC2=N[CH:33]=1)([O-])=O.Br.C(Cl)(=O)CC.C(N(CC)CC)C>C(Cl)Cl.C(O)(=O)C>[N+:1]([C:4]1[CH:5]=[C:10]2[CH:11]([NH:14][C:15](=[O:24])[CH2:28][CH3:33])[CH2:12][O:13][CH2:6][C:7]2=[N:8][CH:9]=1)([O-:3])=[O:2]

Participants

8

Reactant 5

HCID 260Hydrogen BromideHCID 8471TriethylamineHCID 62324Propionyl chlorideHCID 25257027HCID 25257027, compoundHCID 25260448HCID 25260448, compound

Product 1

HCID 68916741HCID 68916741, compoundYield 33%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of benzyl 3,4-dihydro-7-nitro-2H-pyrano[3,2-b]pyridin-3-ylcarbamate and benzyl 6,8-dihydro-3-nitro-5H-pyrano[3,4-b]pyridine-5-ylcarbamate (6.54 g, 26.23 mmol) in CH2Cl2 (55 ml) was stirred at 0° C. and 33% HBr in acetic acid (45 ml) was added. The solution was further stirred at 0° C. for 1 h then at room temperature for 2 h. The solvents were then removed. The crude mixture was dissolved in CH2Cl2/H2O 1/1 (80 ml) and the aqueous mixture adjusted to pH˜10 with 2N NaOH solution. After separation of the layers, the organic phase was washed with H2O (×2), dried over Na2SO4 and evaporated. The residue was dissolved in CH2Cl2 (400 ml) and the solution cooled to 0° C. Propionyl chloride (4.54 ml, 52 mmol) and triethylamine (7.22 ml, 52 mmol) were added and then the mixture was allowed to reach 20° C. and stirred for 4.5 h. The solution was washed successively with 1 N aqueous HCl, saturated aqueous NaHCO3 and water. The organic layer was dried (Na2SO4) and evaporated. Immediate recrystallization in acetone gave a pure fraction of N-(6,8-dihydro-3-nitro-5H-pyrano[3,4-b]pyridin-5-yl)propionamide (2.2 g, 33% for two steps) as a white solid. The remaining mixture was subjected to chromatography on silica gel (heptane:ethyl acetate, 1.5:3.5 then CH2Cl2:CH3OH, 95:5) to afford another portion of N-(6,8-dihydro-3-nitro-5H-pyrano[3,4-b]pyridin-5-yl)propionamide (1.15 mg, 17% for two steps) and N-(3,4-dihydro-7-nitro-2H-pyrano[3,2-b]pyridin-3-yl)propionamide (445 mg, 7% for two steps) as a white solid.

Workup

  1. stirringThe solution was further stirred at 0° C. for 1 h
  2. customThe solvents were then removed
  3. dissolutionThe crude mixture was dissolved in CH2Cl2/H2O 1/1 (80 ml)
  4. customAfter separation of the layers
  5. washthe organic phase was washed with H2O (×2)
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. dissolutionThe residue was dissolved in CH2Cl2 (400 ml)
  9. temperaturethe solution cooled to 0° C
  10. customto reach 20° C.
  11. stirringstirred for 4.5 h
  12. washThe solution was washed successively with 1 N aqueous HCl, saturated aqueous NaHCO3 and water
  13. dry with materialThe organic layer was dried (Na2SO4)
  14. customevaporated
  15. customImmediate recrystallization in acetone

Sources & evidence

ORD record
ord-cb5ce60e565b4349b130f418b9956d42
Source dataset
uspto-grants-2015_03
Patent number
US08969552B2

Reaction notes

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