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

HRID 2169581Notes

Reaction equation

HRID 2169581 reaction equation
[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[NH:8][CH2:7][C@@H: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:22][C:23]1[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[C:25]([CH2:33]Br)[CH:24]=1>CS(C)=O>[Br:22][C:23]1[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[C:25]([CH2:33][N:8]2[CH2:7][C@@H:6]3[CH2:12][O:13][CH2:14][CH2:15][N:5]3[C:4]3[N:3]=[C:2]([Cl:1])[N:11]=[CH:10][C:9]2=3)[CH:24]=1

Participants

5

Reactant 3

HCID 22031079Methyl 4-bromo-2-(bromomethyl)benzoateHCID 23676156Sodium t-butoxideHCID 86670088(R)-2-chloro-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine

Product 1

HCID 86670124(R)-methyl 4-bromo-2-((2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)methyl)benzoateYield 41%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

(R)-2-chloro-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine (200 mg, 0.882 mmol) (PREPARATION x2, 200 mg, 0.882 mmol) was dissolved in DMSO (5 mL). Sodium tert-butoxide (102 mg, 1.059 mmol) was then added to give a brown solution. After 5 minutes, methyl 4-bromo-2-(bromomethyl)benzoate (299 mg, 0.971 mmol) was added dropwise. The reaction was stirred overnight at room temperature, then quenched with aqueous saturated NH4Cl. The reaction mixture was diluted with ethyl acetate and washed with aqueous saturated NH4Cl (3×25 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 (12 g) and eluted using an ethyl acetatehexane gradient. The product was collected and concentrated in vacuo to afford the title compound as a white foam (164 mg, 41%). ESI-MS m/z [M+H]+ calc'd for C18H18BrClN4O3, 453.04; found 453.2.

Workup

  1. customto give a brown solution
  2. customquenched with aqueous saturated NH4Cl
  3. additionThe reaction mixture was diluted with ethyl acetate
  4. washwashed with aqueous saturated NH4Cl (3×25 mL)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. washeluted
  9. customThe product was collected
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9a69de795eae48068d9f4425e0e078fa
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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