Sodium ethoxide → HCID 12044968, compound

HRID 2260989Notes

Reaction equation

HRID 2260989 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 hour, 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 hours 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. temperaturecooled 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 hours 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-1fb7245d1de24b54a353b51bf00ebcaa
Source dataset
uspto-grants-2010_12
Patent number
US07846924B2

Reaction notes

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