Water → Benzo(B)Thiophene

HRID 1700418Notes

Reaction equation

HRID 1700418 reaction equation
COC1C=CC([C:9]2[S:13][C:12]3[CH:14]=[CH:15][CH:16]=[C:17](OC)[C:11]=3[CH:10]=2)=CC=1.FC1C=C(C=C(F)C=1F)C(Cl)=O.[Al+3].[Cl-].[Cl-].[Cl-].O>C(Cl)Cl.CCOC(C)=O>[S:13]1[CH:9]=[CH:10][C:11]2[CH:17]=[CH:16][CH:15]=[CH:14][C:12]1=2

Participants

7

Reactant 4

HCID 962WaterHCID 14844097M-367SHCID 27770233,4,5-Trifluorobenzoyl chlorideHCID 6451240Aluminum(III) Chloride

Product 1

HCID 7221Benzo(B)ThiopheneYield 10.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a well stirred solution of 2-(4′-methoxyphenyl)-4-methoxybenzo[b]thiophene (0.201 g, 0.74 mmol) and 3,4,5-trifluorobenzoyl chloride (0.288 g, 1.48 mmol) in CH2Cl2 (7 mL) was added AlCl3 (0.304 g, 2.22 mmol) portion-wise over a 15 minute period. After 18 h, water was added, and the product was isolated initially with CH2Cl2 and subsequently by extraction with EtOAc. The organic layers were separately washed sequentially with NaHCO3 and brine and then dried over MgSO4. Purification by flash chromatography (silica gel, 80:20 hexane/EtOAc) afforded benzo[b]thiophene (0.032 g, 0.08 mmol, 10%) as a white solid. Recrystallization (Ethanol/hexane/CH2Cl2) yielded a highly pure crystalline sample. 1H-NMR(CDCl3, 360 MHz) δ7.74 (d, J=8.9 Hz, 2H, ArH), 7.70 (d, J=9.3 Hz, 1H, ArH), 7.68 (s, 1H, ArH), 7.43 (dd, J=7.5, 6.6 Hz, 2H, ArH), 7.00 (d, J=8.9 Hz, 2H, ArH), 6.83 (d, J=8.4 Hz, 1H, ArH), 4.09 (s, 3H, —OCH3), 3.87 (S, 3H, —OCH3). 13C-NMR (CDCl3, 90 MHz) 190.5, 160.1, 159.1, 152.3, 150.0, 146.6, 141.3, 134.4, 132.9, 132.1, 127.9, 126.9, 122.4, 114.5, 114.1, 114.1, 114.0, 113.9, 113.8, 56.0, 55.4. HRMS (EI) M+ calcd for C23H15F3O3S 428.0694 found 428.0620. Compound 12A shows an inhibition of tubulin polymerization >40 μM. Biological activity of compound 12A is shown in Table 18.

Workup

  1. washThe organic layers were separately washed sequentially with NaHCO3 and brine
  2. dry with materialdried over MgSO4
  3. customPurification by flash chromatography (silica gel, 80:20 hexane/EtOAc)

Sources & evidence

ORD record
ord-008d1592b26649238c12e632904b6195
Source dataset
uspto-grants-2002_02
Patent number
US06350777B2

Reaction notes

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