Potassium Phosphate, Tribasic → Methyl 7-amino-3a,4-dihydro-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylate

HRID 595112Notes

Reaction equation

HRID 595112 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([O:12][CH2:13][CH:14]2[CH:18]=[CH:17][CH2:16][NH:15]2)[C:5](Br)=[CH:4][CH:3]=1.N1CCC[C@H]1C(O)=O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CS(C)=O.[Cu]I>[NH2:1][C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]2[O:12][CH2:13][CH:14]3[CH:18]=[CH:17][CH2:16][N:15]3[C:5]2=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 86712821methyl 6-amino-3-bromo-2-(2,5-dihydro-1H-pyrrol-2-ylmethoxy)-benzoate2×

Product 1

HCID 86712820Methyl 7-amino-3a,4-dihydro-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylateYield 30%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of methyl 6-amino-3-bromo-2-(2,5-dihydro-1H-pyrrol-2-ylmethoxy)-benzoate (Intermediate 18, 1.64 g), copper (I) iodide (0.095 g), L-proline (0.115 g) and potassium phosphate tribasic (2.13 g) in anhydrous DMSO (10 mL) was evacuated and purged with nitrogen then heated to 90° C., under an atmosphere of nitrogen overnight. The resultant mixture was cooled and partitioned between ethyl acetate and water. The layers were separated and the aqueous layer was extracted with more ethyl acetate. The combined organic layers were dried (MgSO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 10-30% to give methyl 7-amino-3a,4-dihydro-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylate (0.370 g) as a brown oil.

Workup

  1. customwas evacuated
  2. custompurged with nitrogen
  3. temperatureThe resultant mixture was cooled
  4. custompartitioned between ethyl acetate and water
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with more ethyl acetate
  7. dry with materialThe combined organic layers were dried (MgSO4)
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated in vacuo
  10. customthe residue was purified by chromatography on silica
  11. washeluting with a mixture of ethyl acetate and cyclohexane with a gradient of 10-30%

Sources & evidence

ORD record
ord-cefb70105238498b82902ae6fd028b02
Source dataset
uspto-grants-2016_01
Patent number
US09242997B2

Reaction notes

Loading…