Water → LY88074 Trimethyl ether

HRID 1419130Notes

Reaction equation

HRID 1419130 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:13][C:12]3[CH:14]=[C:15]([O:18][CH3:19])[CH:16]=[CH:17][C:11]=3[CH:10]=2)=[CH:5][CH:4]=1.[CH3:20][O:21][C:22]1[CH:30]=[CH:29][C:25]([C:26](Cl)=[O:27])=[CH:24][CH:23]=1.[Al+3].[Cl-].[Cl-].[Cl-].O>C(Cl)Cl.CCOC(C)=O>[CH3:20][O:21][C:22]1[CH:30]=[CH:29][C:25]([C:26]([C:10]2[C:11]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:12]=3[S:13][C:9]=2[C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)=[O:27])=[CH:24][CH:23]=1

Participants

7

Reactant 4

HCID 962WaterHCID 7477p-Anisoyl chlorideHCID 8509416-Methoxy-2-(4-methoxyphenyl)benzo[b]thiopheneHCID 6451240Aluminum(III) Chloride

Product 1

HCID 9953060LY88074 Trimethyl etherYield 78%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a well stirred solution of 2-(4'-methoxyphenyl)-6-methoxybenzo[b]thiophene (0.305 g, 1.13 mmol) and 4-methoxybenzoyl chloride (0.378 g, 2.22 mmol) in CH2Cl2 (45 ml) was added AlCl3 (0.550 g, 4.12 mmol) portion-wise over a 15 minute period. After 1.3 hours, water was added, and the product was isolated initially by extraction with CH2Cl2 and subsequently by extraction with EtOAc. The organic layers were separately washed with brine and then combined and dried over MgSO4. Purification by flash chromatography (silica gel, 70:30 EtOAc/hexanes) afforded the title compound (0.3576 g, 0.88 mmol, 78%) as a pale yellow solid. Recrystallization (EtOAc/hexanes) afforded a highly pure, crystalline sample with mp 119°-120° C. 1H-NMR (CDCl3, 360 MHz): δ=7.77 (d,J=9.0 Hz, 2H, ArH), 7.52 (d,J=8.9 Hz, 1H, ArH), 7.35 (d,J=8.9 Hz, 2H, ArH), 7.31 (d,J=2.3 Hz, 1H, ArH), 6.95 (dd,J=8.9,2.4 Hz, 1H, ArH), 6.76 (d,J=9.0, 2H, ArH), 6.75 (d,J=8.9,2H, ArH), 3.87 (s,3H, --OCH3), 3.79 (s,3H, --OCH3), 3.74 (s, 3H, --OCH3); 13C-NMR (CDCl3, 90 MHz): δ=193.2, 193,7, 159.7, 157.6, 142.4, 140.0, 134.0, 132.2, 130.6, 130.4, 130.2, 126.0, 124.0, 114.7, 114.0, 113.6, 104.5, 55.6, 55.4, 55.2. HRMS (El) M+ calcd for C24H20O4S, 404.1082, found 404.1059. Anal. Calcd for C24H20O4S: C, 71.27; H, 4.98; S, 7.93. Found: C, 71.39; H, 4.98; S, 7.90.

Workup

  1. washThe organic layers were separately washed with brine
  2. dry with materialdried over MgSO4
  3. customPurification by flash chromatography (silica gel, 70:30 EtOAc/hexanes)

Sources & evidence

ORD record
ord-e8df634c9d84460cb2cd2f1c8a5d36c4
Source dataset
uspto-grants-1999_03
Patent number
US05886025

Reaction notes

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