p-Anisoyl chloride → LY88074 Trimethyl ether

HRID 2393733Notes

Reaction equation

HRID 2393733 reaction equation
[C:1](Cl)(=[O:10])[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.[CH3:12][O:13][C:14]1[CH:15]=[CH:16][C:17]2[CH:21]=[C:20]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=3)[S:19][C:18]=2[CH:30]=1.[Cl-].[Al+3].[Cl-].[Cl-]>C(Cl)Cl>[CH3:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([C:1]([C:21]2[C:17]3[CH:16]=[CH:15][C:14]([O:13][CH3:12])=[CH:30][C:18]=3[S:19][C:20]=2[C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)=[O:10])=[CH:3][CH:4]=1

Participants

5

Reactant 3

HCID 7477p-Anisoyl chlorideHCID 8509416-Methoxy-2-(4-methoxyphenyl)benzo[b]thiopheneHCID 6451240Aluminum(III) Chloride

Product 1

HCID 9953060LY88074 Trimethyl ether

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of p-anisoyl chloride (1.54 g, 9.00 mmol) stirring at ambient temperature in anhydrous methylene chloride (100 ml) was added 6-methoxy-2-(4-methoxyphenyl)benzo [b]thiophene (1.62 g, 6.00 mmol). The resulting mixture was cooled to 0° C. and aluminum chloride (1.20 g, 9.00 mmol) was added in small portions over a five minute period. After 1 hour, the reaction mixture was poured into ice water (150 mL) and extracted with methylene chloride. The combined organic extracts were washed with 1N sodium hydroxide, water, brine, dried (magnesium sulfate), filtered, and concentrated. The resulting material was purified by flash chromatography (silica gel, 30% ethyl acetate in hexanes) giving 2.25 g (93%) of a the desired product as a light yellow solid. The product was further purified by recrystallization from acetone/methanol to give 2.11 g (87%): 1H NMR (300 MHz, DMSO-d6) δ 7.64-7.69 (m,3H), 7.29-7.32 (m, 3H). 6.86-7.00 (m, 5H), 3.83 (s, 3H) 3.76 (s, 3H); 13C NMR (75.5 MHz, DMSO-d6) δ 192.0, 163.6, 159.5, 157.4, 141.0, 139.4, 133.2, 131.8, 130.0, 129.6, 125.2, 123.3, 115.0, 114.4, 114.1, 105.1, 55.5, 55.1; IR (CHCl3) 3020, 3015, 2970, 2940, 2840, 1600, 1475, 1253, 1218, 1167; MS (FD) 404 (M+); Anal. Calcd for C24 H20O4S: C, 71.27; H, 4.98; S, 7.93; O, 15.82. Found: C, 71.50; H, 5.00; S, 7.98; O, 15.77.

Workup

  1. extractionextracted with methylene chloride
  2. washThe combined organic extracts were washed with 1N sodium hydroxide, water, brine
  3. dry with materialdried (magnesium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting material was purified by flash chromatography (silica gel, 30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-bab5ec2e88444c1f8a80ac39a138e526
Source dataset
uspto-grants-1998_09
Patent number
US05808061

Reaction notes

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