Triphenyl phosphite → (S)-methyl 6-oxo-6,6a,7,8-tetrahydro-5H-azeto[1,2-a]pyrido[3,2-e]pyrazine-3-carboxylate

HRID 1644984

Reaction equation

HRID 1644984 reaction equation
C[O:2][C:3]([C@@H:5]1[CH2:8][CH2:7][N:6]1[C:9]1[C:18]([N+:19]([O-])=O)=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][N:10]=1)=O.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>ClCCl.[NH4+].[O-][V](=O)=O.[Pt]>[O:2]=[C:3]1[NH:19][C:18]2[CH:17]=[C:12]([C:13]([O:15][CH3:16])=[O:14])[CH:11]=[N:10][C:9]=2[N:6]2[CH2:7][CH2:8][C@@H:5]12

Participants

6

Reactant 2

HCID 7540Triphenyl phosphiteHCID 58324421HCID 58324421, compound

Product 1

HCID 58324364(S)-methyl 6-oxo-6,6a,7,8-tetrahydro-5H-azeto[1,2-a]pyrido[3,2-e]pyrazine-3-carboxylateYield 82.1%

Reagents, catalysts & solvents 3

HCID 23939PlatinumCatalystHCID 516859Ammonium metavanadateCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

(S)-methyl 6-(2-(methoxycarbonyl)azetidin-1-yl)-5-nitronicotinate (0.90 g, 3.05 mmol) was dissolved in dichloromethane (Volume: 15.24 ml) and to this solution was added triphenyl phosphite (9.46 mg, 0.030 mmol), ammonium metavanadate (0.021 g, 0.183 mmol) and Pt/C (5% wt.) (0.119 g, 0.030 mmol). The reaction mixture was hydrogenated at 100 psi at 25° C. for 2 h. LCMS showed complete conversion of the starting material to the corresponding amine, but no cyclization product was observed. The reaction mixture was filtered through a short plug of celite and the plug and precipitate were washed well with dichloromethane (30 mL) and methanol (20 mL). The combined filtrates were concentrated in vacuo (LC: CR1) and dissolved in AcOH (5 mL) (LC: AA-rt). This solution was heated to 80° C. for 5 min (LCMS—AA-90C-5 min—complete conversion to the desired product) and concentrated in vacuo. The residue was crystallized with ethyl ether (20 mL) and sonicated until a fine suspension was obtained The precipitate was filtered off and dried in vacuum to afford (S)-methyl 6-oxo-6,6a,7,8-tetrahydro-5H-azeto[1,2-a]pyrido[3,2-e]pyrazine-3-carboxylate (0.5840, 2.504 mmol, 82% yield) as a light pink solid. [M+H] calc'd for C11H11N3O3, 234; found, 234.

Workup

  1. filtrationThe reaction mixture was filtered through a short plug of celite
  2. washthe plug and precipitate were washed well with dichloromethane (30 mL) and methanol (20 mL)
  3. concentrationThe combined filtrates were concentrated in vacuo (LC: CR1)
  4. dissolutiondissolved in AcOH (5 mL) (LC: AA-rt)
  5. concentrationconcentrated in vacuo
  6. customThe residue was crystallized with ethyl ether (20 mL)
  7. customsonicated until a fine suspension
  8. customwas obtained The precipitate
  9. filtrationwas filtered off
  10. customdried in vacuum

Sources & evidence

ORD record
ord-7e68aa474f1d491285bb4f46b12cd0d7
Source dataset
uspto-grants-2012_02
Patent number
US08124606B2

Linked notes

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