Hydrochloric Acid → 1-(2-(6-(2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)-7-oxo-2,6-diazabicyclo(3.2.1)oct-2-yl)ethyl)-7-methoxyquinoxalin-2(1H)-one

HRID 40006Notes

Reaction equation

HRID 40006 reaction equation
CO.[O:3]1[C:12]2[CH:11]=[C:10]([CH2:13][NH:14][CH:15]3[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][N:23]4[C:32]5[C:27](=[CH:28][CH:29]=[C:30]([O:33][CH3:34])[CH:31]=5)[N:26]=[CH:25][C:24]4=[O:35])[CH:17]([C:36]([O:38]C)=O)[CH2:16]3)[N:9]=[CH:8][C:7]=2[O:6][CH2:5][CH2:4]1.[OH-].[Na+].Cl>C(OCC)C.CCCCCC.C(OCC)(=O)C.O>[O:3]1[C:12]2[CH:11]=[C:10]([CH2:13][N:14]3[C:36](=[O:38])[CH:17]4[CH2:16][CH:15]3[CH2:20][CH2:19][N:18]4[CH2:21][CH2:22][N:23]3[C:32]4[C:27](=[CH:28][CH:29]=[C:30]([O:33][CH3:34])[CH:31]=4)[N:26]=[CH:25][C:24]3=[O:35])[N:9]=[CH:8][C:7]=2[O:6][CH2:5][CH2:4]1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium Hydroxide2×HCID 59398301HCID 59398301, compound

Product 1

HCID 675395261-(2-(6-(2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)-7-oxo-2,6-diazabicyclo(3.2.1)oct-2-yl)ethyl)-7-methoxyquinoxalin-2(1H)-oneYield 16%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 5 mL of a methanol solution containing 60 mg of methyl 4-((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)amino)-1-(2-(7-methoxy-2-oxoquinoxalin-1(2H)-yl)ethyl)piperidine-2-carboxylate, 0.2 mL of 20% aqueous sodium hydroxide solution was added at room temperature, and stirred for 1 hour and 10 min. Further, 0.5 mL of 20% aqueous sodium hydroxide solution was added at room temperature, and stirred at the sane temperature for 1 hour and 50 min. The reaction mixture was adjusted to pH 6.2 with 2 mol/L hydrochloric acid under water-cooling, the solvent was removed under reduced pressure, water, ethyl acetate and diethyl ether were added, and the resulting solid (A′) was filtered. Also, the solvent of the filtrate (B′) was removed under reduced pressure. To the residue thus obtained, water, ethyl acetate and diethyl ether were added, the organic layer was separated, and the solvent was removed under reduced pressure. To the residue thus obtained, hexane and diethyl ether were added, and the resulting solid (B) was filtered to give 9 mg of 1-(2-(6-(2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)-7-oxo-2,6-diazabicyclo(3.2.1)oct-2-yl)ethyl)-7-methoxyquinoxalin-2(1H)-one as a pale yellow solid.

Workup

  1. additionwas added at room temperature
  2. stirringstirred at the sane temperature for 1 hour and 50 min
  3. temperaturecooling
  4. customthe solvent was removed under reduced pressure, water, ethyl acetate and diethyl ether
  5. additionwere added
  6. filtrationthe resulting solid (A′) was filtered
  7. customAlso, the solvent of the filtrate (B′) was removed under reduced pressure
  8. customTo the residue thus obtained
  9. customthe organic layer was separated
  10. customthe solvent was removed under reduced pressure
  11. customTo the residue thus obtained
  12. filtrationthe resulting solid (B) was filtered

Sources & evidence

ORD record
ord-882114b8136c4fb5b51216e543ba5f6d
Source dataset
uspto-grants-2013_09
Patent number
US08524738B2

Reaction notes

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