Oxalyl chloride → 6-Benzyloxy-2-(dimethylamino)benzo[b]thiophen-3-yl 3-Methoxy-4-triisopropylsilyloxyphenyl Ketone

HRID 1387105Notes

Reaction equation

HRID 1387105 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][Si:13]([CH:20]([CH3:22])[CH3:21])([CH:17]([CH3:19])[CH3:18])[CH:14]([CH3:16])[CH3:15])[C:6](O)=[O:7].C(Cl)(=O)C(Cl)=O.[CH2:29]([O:36][C:37]1[CH:38]=[CH:39][C:40]2[CH:44]=[C:43]([N:45]([CH3:47])[CH3:46])[S:42][C:41]=2[CH:48]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C([O-])(O)=O.[Na+]>ClC(Cl)C.CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:6]([C:44]2[C:40]3[CH:39]=[CH:38][C:37]([O:36][CH2:29][C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=4)=[CH:48][C:41]=3[S:42][C:43]=2[N:45]([CH3:46])[CH3:47])=[O:7])[CH:9]=[CH:10][C:11]=1[O:12][Si:13]([CH:17]([CH3:19])[CH3:18])([CH:20]([CH3:21])[CH3:22])[CH:14]([CH3:15])[CH3:16]

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 106129946-Benzyloxy-2-dimethylaminobenzo[b]thiopheneHCID 183185063-Methoxy-4-triisopropylsilyloxybenzoic acid

Product 1

HCID 183185456-Benzyloxy-2-(dimethylamino)benzo[b]thiophen-3-yl 3-Methoxy-4-triisopropylsilyloxyphenyl Ketone

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 63651,1-DichloroethaneSolvent

Procedure

A slurry of 3-methoxy-4-triisopropylsilyloxybenzoic acid (9.75 g, 30 mmol; Part A) in 300 mL of dichloroethane and 1 drop of DMF was treated with oxalyl chloride (13.1 mL, 150 mmol) and stirred overnight at ambient temperature. The reaction mixture was concentrated in vacuo and suspended in 300 mL of chlorobenzene. 6-Benzyloxy-2-(N,N-dimethylamino)benzo[b]thiophene (8.5 g, 30 mmol) was added, and the resulting mixture was heated at 105° C. for 5 h. After cooling to ambient temperature, the reaction mixture was poured into 500 mL of saturated aqueous NaHCO3 solution. The aqueous layer was extracted with CHCl3 (3×150 mL). The combined organics were dried over K2CO3, filtered and concentrated in vacuo. Purification by flash chromatography (SiO2; gradient of 5% to 10% EtOAc in hexanes) afforded 6.05 g (10.3 mmol; 34%) of the title compound.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. temperaturethe resulting mixture was heated at 105° C. for 5 h
  3. temperatureAfter cooling to ambient temperature
  4. extractionThe aqueous layer was extracted with CHCl3 (3×150 mL)
  5. dry with materialThe combined organics were dried over K2CO3
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by flash chromatography (SiO2; gradient of 5% to 10% EtOAc in hexanes)

Sources & evidence

ORD record
ord-31436a8b0fbe4678b9e7f8a21b2a5e91
Source dataset
uspto-grants-2001_07
Patent number
US06265575B1

Reaction notes

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