Water → Benzo(B)Thiophene

HRID 1700419Notes

Reaction equation

HRID 1700419 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.COC1C=C(C=C(OC)C=1OC)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 78282Benzoyl chloride, 3,4,5-trimethoxy-HCID 14844097M-367SHCID 6451240Aluminum(III) Chloride

Product 1

HCID 7221Benzo(B)ThiopheneYield 7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a well stirred solution of 2-(4′-methoxyphenyl)-4-methoxybenzo[b]thiophene (0.200 g, 0.74 mmol) and 3,4,5-trimethoxybenzoyl chloride (0.1 84 g, 0.74 mmol) in CH2Cl2 (7 mL) was added AlCl3 (0.200 g, 1.48 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, 70:30 hexane/EtOAc) afforded benzo[b]thiophene (0.023 g, 0.05 mmol, 7%) as a white solid. Recrystallization (Ethanol/hexane/CH2Cl2)yielded a highly pure crystalline sample. 1H-NMR (CDCl3, 360 MHz) δ7.80 (d, J=8.4 Hz, 1H, ArH), 7.73 (d, J=8.8 Hz, 2H, ArH), 7.66 (s, 1H, ArH), 7.02 (s, 2H, ArH), 6.96 (d, J=8.8 Hz, 2H, ArH), 6.70 (d, J=8.3 Hz, 1H, arH), 4.08 (s, 3H, —OCH3), 3.95 (s, 3H, —OCH3), 3.91 (s, 6H, —OCH3), 3.87 (S, 3H, —OCH3), HRMS (EI) M+ calcd for C26H24O6S 464.1294, found 464.1310. Anal. Calcd for C26H24O6S: C, 67.23; H, 5.21; S, 6.90. Found C, 67.19; H, 5.26; S, 6.87. Compound 13A shows an inhibition of tubulin polymerization >40 μM. Biological activity of compound 13A is shown in Table 19.

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, 70:30 hexane/EtOAc)

Sources & evidence

ORD record
ord-7f516642c6d34337b61e9204231496ff
Source dataset
uspto-grants-2002_02
Patent number
US06350777B2

Reaction notes

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