Sulfuric Acid → Methyl 2-bromo-4-(3,4-dichlorophenyl)-7-oxo-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-5-carboxylate

HRID 1615554Notes

Reaction equation

HRID 1615554 reaction equation
S(=O)(=O)(O)O.C(Cl)(Cl)Cl.[Br:10][C:11]1[S:15][C:14]2[C:16](=[O:31])[CH:17]([C:27]([O:29][CH3:30])=[O:28])[CH:18]([C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([Cl:26])[CH:20]=3)[C:13]=2[CH:12]=1.[N-:32]=[N+]=[N-].[Na+]>>[Br:10][C:11]1[S:15][C:14]2[C:16](=[O:31])[NH:32][CH:17]([C:27]([O:29][CH3:30])=[O:28])[CH:18]([C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([Cl:26])[CH:20]=3)[C:13]=2[CH:12]=1

Participants

5

Reactant 4

HCID 1118Sulfuric AcidHCID 6212ChloroformHCID 33557Sodium AzideHCID 68183335methyl 2-bromo-4-(3,4-dichlorophenyl)-6-oxo-5,6-dihydro-4H-cyclopenta[b]thiophene-5-carboxylate

Product 1

HCID 68183119Methyl 2-bromo-4-(3,4-dichlorophenyl)-7-oxo-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-5-carboxylateYield 48.3%

Conditions

Temperature
15 °C

Procedure

To a mixture of sulfuric acid (5.01 mL, 94.0 mmol) and chloroform (49.6 mL, 6.20E2 mmol) was added methyl 2-bromo-4-(3,4-dichlorophenyl)-6-oxo-5,6-dihydro-4H-cyclopenta[b]thiophene-5-carboxylate (5.01 g, 11.9 mmol) followed by sodium azide (3.72 g, 57.2 mmol) in small portions over 3 h with vigorous stirring at 15° C. After addition, the mixture was stirred at rt overnight. The reaction was quenched by ice, basified with sodium bicarbonate, and extracted with DCM. The DCM layer was washed with brine, followed by sodium bicarbonate solution and brine. Dried and evaporated to afford crude product which was purified by silica gel chromatography to afford product as off-white solid (2.50 g, 48.2%). LCMS: (AA) ES+: 435, 437, 1H NMR (400 MHz, CDCl3) δ 7.43-7.38 (m, 1H), 7.28 (d, J=2.2 Hz, 1H), 7.00 (dd, J=8.3, 2.2 Hz, 1H), 6.77 (s, 1H), 5.92 (t, J=9.3 Hz, 1H), 4.67 (d, J=3.3 Hz, 1H), 4.28 (t, J=3.6 Hz, 1H), 3.76 (s, 3H).

Workup

  1. additionAfter addition
  2. stirringthe mixture was stirred at rt overnight
  3. customThe reaction was quenched by ice
  4. extractionextracted with DCM
  5. washThe DCM layer was washed with brine
  6. customDried
  7. customevaporated
  8. customto afford crude product which
  9. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-92fbce7773704c0283a70477f906bea4
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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