Methyl 4-(bromomethyl)benzoate → methyl 4-((2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)methyl)benzoate

HRID 1631705Notes

Reaction equation

HRID 1631705 reaction equation
[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[NH:8][CH2:7][CH:6]3[CH2:12][O:13][CH2:14][CH2:15][N:5]3[C:4]=2[N:3]=1.CC(C)([O-])C.[Na+].Br[CH2:23][C:24]1[CH:33]=[CH:32][C:27]([C:28]([O:30][CH3:31])=[O:29])=[CH:26][CH:25]=1>CS(C)=O.C(OCC)(=O)C>[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:23][C:24]3[CH:33]=[CH:32][C:27]([C:28]([O:30][CH3:31])=[O:29])=[CH:26][CH:25]=3)[CH2:7][CH:6]3[CH2:12][O:13][CH2:14][CH2:15][N:5]3[C:4]=2[N:3]=1

Participants

6

Reactant 3

HCID 256687Methyl 4-(bromomethyl)benzoateHCID 23676156Sodium t-butoxideHCID 86670087HCID 86670087, compound

Product 1

HCID 86670091methyl 4-((2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)methyl)benzoateYield 23%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

2-Chloro-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine (PREPARATION x2, 350 mg, 1.544 mmol) was dissolved in DMSO (10 mL). Sodium tert-butoxide (223 mg, 2.316 mmol) was added, followed 5 minutes later by the addition of methyl 4-(bromomethyl)benzoate (531 mg, 2.316 mmol) to give a brown suspension. The reaction mixture was heated to 100° C. in a microwave on high absorbance for 30 minutes. The reaction mixture was diluted with ethyl acetate and washed with aqueous saturated NH4Cl (2×15 mL) and brine (2×15 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The crude product was loaded onto an ISCO® silica gel cartridge (24 g) and eluted using an ethyl acetate/hexane gradient. The product was collected and concentrated in vacuo to afford the title compound as a yellow oil (133 mg, 23%). ESI-MS m/z [M+H]+ calc'd for C18H19ClN4O3, 375.1. found 375.4.

Workup

  1. customto give a brown suspension
  2. washwashed with aqueous saturated NH4Cl (2×15 mL) and brine (2×15 mL)
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. washeluted
  7. customThe product was collected
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-71f9b9b938624c6b959164962fb1cd23
Source dataset
uspto-grants-2014_07
Patent number
US08791107B2

Reaction notes

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