Sodium ethoxide → 5-(4,4-Dimethyl-2-thioxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1H-pyrrole-2-carbonitrile

HRID 2400401Notes

Reaction equation

HRID 2400401 reaction equation
[C:1]([C:3]1[N:4](C(OC(C)(C)C)=O)[C:5]([C:8]2[CH:9]=[CH:10][C:11]3[NH:16][C:15](=[S:17])[O:14][C:13]([CH3:19])([CH3:18])[C:12]=3[CH:20]=2)=[CH:6][CH:7]=1)#[N:2].CC[O-].[Na+]>C1COCC1.CCO>[CH3:18][C:13]1([CH3:19])[C:12]2[CH:20]=[C:8]([C:5]3[NH:4][C:3]([C:1]#[N:2])=[CH:7][CH:6]=3)[CH:9]=[CH:10][C:11]=2[NH:16][C:15](=[S:17])[O:14]1

Participants

5

Reactant 2

HCID 2723922Sodium ethoxideHCID 9977271HCID 9977271, compound

Product 1

HCID 103790915-(4,4-Dimethyl-2-thioxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1H-pyrrole-2-carbonitrileYield 73.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of tert-butyl 2-cyano-5-(4,4-dimethyl-2-thioxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1H-pyrrole-1-carboxylate (0.5 g, 1.3 mmol, 1 eq) in THF (5 mL) was added NaOEt (0.27 g, 3.9 mmol, 3 eq) in EtOH (5 mL) and the reaction was heated to 80° C. for 2 h. The solvents were removed in vacuo and the residue partitioned between ethyl acetate (100 mL) and water (100 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (100 mL). The organic layers were combined, washed with brine (50 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by flash column chromatography (10% ethyl acetate/hexane) gave the title compound (0.27 g, 73%) as a brown powder, mp 261-262° C. 1H NMR (DMSO-d6) δ 1.68 (s, 6H), 6.72-6.73 (m, 1H), 6.99-7.01 (m, 1H), 7.06 (d, 1H, J=7.9 Hz), 7.66-7.70 (m, 2H), 12.26 (s, 1H), 12.62 (s, 1H); MS (ESI) [M−H]−=282; Anal. Calcd. For C15H13N3OS: C, 63.58; H, 4.62; N, 14.83. Found: C, 63.25; H, 4.78; N, 15.11.

Workup

  1. customThe solvents were removed in vacuo
  2. customthe residue partitioned between ethyl acetate (100 mL) and water (100 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (100 mL)
  5. washwashed with brine (50 mL)
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by flash column chromatography (10% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-dc39272066a24a3fb025ab5cfae593e3
Source dataset
uspto-grants-2014_08
Patent number
US08796266B2

Reaction notes

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