Hydrochloric Acid → HCID 68771517, compound

HRID 1947482Notes

Reaction equation

HRID 1947482 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:9][C:8]2[CH:10]=[C:11]([O:14][CH3:15])[CH:12]=[CH:13][C:7]=2[CH:6]=1)=[O:4].B(Br)(Br)Br.C([O-])([O-])=O.[Cs+].[Cs+].ClC1[S:28][C:29]2[CH:35]=[CH:34][CH:33]=[CH:32][C:30]=2[N:31]=1.Cl>C(Cl)Cl.CCOC(C)=O.O>[CH3:1][O:2][C:3]([C:5]1[S:9][C:8]2[CH:10]=[C:11]([O:14][C:15]3[S:28][C:29]4[CH:35]=[CH:34][CH:33]=[CH:32][C:30]=4[N:31]=3)[CH:12]=[CH:13][C:7]=2[CH:6]=1)=[O:4]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 119872-ChlorobenzothiazoleHCID 25134Boron tribromideHCID 534861116-Methoxy-benzo[B]thiophene-2-carboxylic acid methyl ester

Product 1

HCID 68771517HCID 68771517, compoundYield 5.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a cooled (−78° C.) solution of 6-methoxy-benzo[b]thiophene-2-carboxylic acid methyl ester (4.7 g, 21 mmol) in DCM (210 mL) was added BBr3 (6.0 mL, 15.9 g, 63 mmol) dropwise and the reaction mixture was allowed to warm (rt, 4 h). The reaction mixture was cooled (0° C.), diluted with EtOAc (200 mL) and treated with H2O (25 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (2×100 mL). The organic layer was dried, filtered and concentrated in vacuo. The resulting residue was dissolved in MeCN (150 mL) and treated with Cs2CO3 (9.8 g, 30 mmol) and 2-chlorobenzothiazole (1.9 mL, 2.5 g, 15 mmol) and the reaction mixture was heated (60° C., 4 h). The reaction mixture was cooled (rt) and treated with 1 M HCl (50 mL) and partitioned between EtOAc (100 mL) and H2O (50 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (2×100 mL). The organic layer was dried, filtered and concentrated in vacuo. The resulting residue was purified by silica gel flash chromatography using EtOAc:hexane (0-60%) to provide the title compound as a colorless foam (0.27 g, 5%). MS (ESI): mass calcd. for O11H10O3S2, 341.0; m/z found, 342.0 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.07 (s, J=0.6, 1H), 7.93 (dd, J=5.4, 3.2, 2H), 7.75 (dd, J=8.1, 0.6, 1H), 7.70 (dd, J=8.0, 0.7, 1H), 7.50-7.37 (m, 2H), 7.35-7.27 (m, 1H), 3.96 (s, 3H).

Workup

  1. temperatureThe reaction mixture was cooled (0° C.)
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with EtOAc (2×100 mL)
  4. customThe organic layer was dried
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe resulting residue was dissolved in MeCN (150 mL)
  8. temperaturethe reaction mixture was heated (60° C., 4 h)
  9. temperatureThe reaction mixture was cooled (rt)
  10. custompartitioned between EtOAc (100 mL) and H2O (50 mL)
  11. customThe organic layer was separated
  12. extractionthe aqueous layer was extracted with EtOAc (2×100 mL)
  13. customThe organic layer was dried
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. customThe resulting residue was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-3215ef8d4e644cbba6f0221c9e5cd752
Source dataset
uspto-grants-2013_03
Patent number
US08399465B2

Reaction notes

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