Hydrogen Peroxide → 3-benzyl-2-(hydroxymethyl)-4H-pyrido[1,2-a]pyrimidin-4-one

HRID 1784463Notes

Reaction equation

HRID 1784463 reaction equation
[OH:1][CH2:2][C:3]1[N:4]=[C:5]2[CH:14]=[CH:13][CH:12]=[CH:11][N:6]2[C:7](=[O:10])[C:8]=1I.[O-]P([O-])([O-])=O.[K+].[K+].[K+].B1([CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)C2CCCC1CCC2.[OH-].[Na+].OO>CN(C=O)C.C(OCC)(=O)C.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[CH2:32]([C:8]1[C:7](=[O:10])[N:6]2[CH:11]=[CH:12][CH:13]=[CH:14][C:5]2=[N:4][C:3]=1[CH2:2][OH:1])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

9

Reactant 5

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 62657Potassium Phosphate, TribasicHCID 41509249-Benzyl-9-borabicyclo(3.3.1)nonaneHCID 596541742-(Hydroxymethyl)-3-iodo-4h-pyrido[1,2-a]pyrimidin-4-one

Product 1

HCID 596541663-benzyl-2-(hydroxymethyl)-4H-pyrido[1,2-a]pyrimidin-4-oneYield 91%

Reagents, catalysts & solvents 3

HCID 53485975CID 53485975CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent5×

Conditions

Temperature
80 °C

Procedure

A mixture of 4.0 g (13.24 mmol) of the product from Step 4 (14), 1.0 g (1.32 mmol) of dichloro[1,1′-bis(diphenylphosphino)ferrocene] palladium(II) dichloromethane adduct, and 8.4 g (39.72 mmol) of K3PO4 in 30 mL of DMF was heated to 80° C. To the resulting solution was added dropwise 40 mL (19.9 mmol) of B-Benzyl-9-BBN and stirred at 80° C. under nitrogen for 12 hours. The reaction was then cooled to 0° C. and excess 1N NaOH was added to the reaction mixture. Excess 30% H2O2 was then added to the mixture at 0° C. resulting in significant gas evolution. Stirring continued for at least one additional hour or until gas ceased to evolve. The mixture was extracted with ethyl acetate (3×) and washed with saturated Na2O3S2 and brine. The organic layers were combined, dried over MgSO4 and activated carbon, and the solvent was removed in vacuo. The resulting material was subjected to flash chromatography on a 10 cm column. Elution with a gradient of 100% hexanes, 20% ethyl acetate in hexanes, 33% ethyl acetate in hexanes, 43% ethyl acetate in hexanes, 50% ethyl acetate in hexanes, 57% ethyl acetate in hexanes, 67% ethyl acetate in hexanes, and 100% ethyl acetate yielded 3.2 g (12.0 mmol, 91%) of 3-benzyl-2-(hydroxymethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (15) as a pale yellow solid.

Workup

  1. temperatureThe reaction was then cooled to 0° C.
  2. customresulting in significant gas evolution
  3. stirringStirring
  4. extractionThe mixture was extracted with ethyl acetate (3×)
  5. washwashed with saturated Na2O3S2 and brine
  6. dry with materialdried over MgSO4 and activated carbon
  7. customthe solvent was removed in vacuo
  8. washElution with a gradient of 100% hexanes, 20% ethyl acetate in hexanes, 33% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-465f2de5c44f4eafb490bd0a27c9b5c6
Source dataset
uspto-grants-2009_03
Patent number
US07504405B2

Reaction notes

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