1,2-Dibromopropane → Ethyl 6,7-dihydro-5H-pyrazolo[5,1-B][1,3]oxazine-3-carboxylate

HRID 1697460Notes

Reaction equation

HRID 1697460 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7](=[O:11])[NH:8][NH:9][CH:10]=1)=[O:5])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:19][CH:20](Br)[CH3:21]>CN(C)C=O>[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[N:9][N:8]2[CH2:21][CH2:20][CH2:19][O:11][C:7]=12)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 65531,2-DibromopropaneHCID 11430Potassium CarbonateHCID 238933ethyl 3-hydroxy-1H-pyrazole-4-carboxylate

Product 1

HCID 52228126Ethyl 6,7-dihydro-5H-pyrazolo[5,1-B][1,3]oxazine-3-carboxylateYield 58.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

3-Oxo-2,3-dihydro-1H-pyrazole-4-carboxylic acid ethyl ester (13.2 g, 84.5 mmol), potassium carbonate (50 g, 0.3 mol) and N,N-dimethylformamide (500 mL) were combined in a 250 mL round bottom flask, and the mixture was heated to 130° C. 1,2-Dibromo-propane (10.4 mL, 0.10 mol) was added. After 30 minutes, the mixture was partitioned between DCM and water. The aqueous layer was extracted with DCM and the combined organics were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The yellow solid was purified by column chromatography (DCM/MeOH) to afford the ester (9.67 g, 58%) as a solid. 1H NMR (400 MHz, DMSO-d6) δ7.62 (s, 1H), 4.41-4.38 (m, 2H), 4.13 (q, 2H), 4.08 (t, 2H, J=6.03 Hz), 2.21-2.15 (m, 2H), 1.21 (t, 3H, J=7.09 Hz).

Workup

  1. customthe mixture was partitioned between DCM and water
  2. extractionThe aqueous layer was extracted with DCM
  3. washthe combined organics were washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe yellow solid was purified by column chromatography (DCM/MeOH)

Sources & evidence

ORD record
ord-834678615d694e158ca0aacc84ef59ae
Source dataset
uspto-grants-2012_04
Patent number
US08163901B2

Reaction notes

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