Sodium ethoxide → HCID 12044968, compound

HRID 1609873Notes

Reaction equation

HRID 1609873 reaction equation
[Br:1][C:2]1[CH:6]=[C:5]([C:7]#[N:8])[N:4]([CH3:9])[C:3]=1[C:10]1[CH:11]=[CH:12][C:13]2[N:18](C(OC(C)(C)C)=O)[C:17](=[O:26])[O:16][C:15]([CH3:28])([CH3:27])[C:14]=2[CH:29]=1.[O-]CC.[Na+]>C1COCC1.C(O)C>[Br:1][C:2]1[CH:6]=[C:5]([C:7]#[N:8])[N:4]([CH3:9])[C:3]=1[C:10]1[CH:11]=[CH:12][C:13]2[NH:18][C:17](=[O:26])[O:16][C:15]([CH3:27])([CH3:28])[C:14]=2[CH:29]=1

Participants

5

Reactant 2

HCID 2723922Sodium ethoxideHCID 22260273HCID 22260273, compound

Product 1

HCID 12044968HCID 12044968, compoundYield 54.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

A solution of tert-butyl 6-(3-bromo-5-cyano-1-methyl-1H-pyrrol-2-yl)-4,4-dimethyl-2-oxo-2H-3,1-benzoxazine-1(4H)-carboxylate (1 eq, 0.4 g, 0.87 mmol) in THF was added to a solution of sodium ethoxide (3 eq, 0.18 g, 2.6 mmol) in ethanol (10 mL). The solution was heated at 80° C. for 1 h then cooled to room temperature and concentrated in vacuo. The residue was dissolved in THF (10 mL) and 4N HCl (10 mL) was added. After heating to 60° C. for 16 h the solution was cooled, poured into water and the layers were separated. The aqueous layer was extracted with ethyl acetate (3×10 mL) and the combined organic layer was washed with brine, dried over MgSO4 and concentrated in vacuo. The product, 4-bromo-5-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-3, 1-benzoxazin-6-yl)-1-methyl-1H-pyrrole-2-carbonitrile (0.17 g, 54%) was obtained by crystallization from 20% ethyl acetate/hexane. 1H NMR (300 MHz, d6-DMSO) δ 1.64 (s, 6H), 3.62 (s, 3H), 7.02 (d, 1H, J=8.2 Hz), 7.34 (s, 1H), 7.35 (dd, 1H, J=1.3, 8.2 Hz), 7.40 (s, 1H), 10.47 (s, 1H). MS (ESI (−)) m/z 358/360 (M−H)−. Anal. calcd for C16H14N3O2Br, C, 53.4, H, 3.92, N, 11.7. Found, C, 52.6, H, 3.82, N, 11.2.

Workup

  1. temperaturethen cooled to room temperature
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in THF (10 mL)
  4. addition4N HCl (10 mL) was added
  5. temperatureAfter heating to 60° C. for 16 h the solution
  6. temperaturewas cooled
  7. additionpoured into water
  8. customthe layers were separated
  9. extractionThe aqueous layer was extracted with ethyl acetate (3×10 mL)
  10. washthe combined organic layer was washed with brine
  11. dry with materialdried over MgSO4
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-46cc2a84dc864afa9cf37385daee6b83
Source dataset
uspto-grants-2006_01
Patent number
US06982261B2

Reaction notes

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