Sulfuric Acid → HCID 86617503, compound

HRID 2081115Notes

Reaction equation

HRID 2081115 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7]2[S:15][CH:14]=[C:13]([CH2:16][O:17][C:18]3[CH:23]=[C:22]([C:24]4[N:28]([CH2:29]C5C=CC(OC)=CC=5)[C:27](C)=[N:26][N:25]=4)[CH:21]=[CH:20][C:19]=3[CH3:39])[C:8]=2[C:9]([Cl:12])=[N:10][CH:11]=1)=[O:5])[CH3:2].FC(F)(F)C(O)=O.C1(OC)C=CC=CC=1.S(=O)(=O)(O)O>>[CH2:1]([O:3][C:4]([C:6]1[C:7]2[S:15][CH:14]=[C:13]([CH2:16][O:17][C:18]3[CH:23]=[C:22]([C:24]4[N:28]([CH3:29])[CH:27]=[N:26][N:25]=4)[CH:21]=[CH:20][C:19]=3[CH3:39])[C:8]=2[C:9]([Cl:12])=[N:10][CH:11]=1)=[O:5])[CH3:2]

Participants

5

Reactant 4

HCID 1118Sulfuric AcidHCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 24810383HCID 24810383, compound

Product 1

HCID 86617503HCID 86617503, compound

Procedure

A mixture of 4-chloro-3-{5-[4-(4-methoxy-benzyl)-5-methyl-4H-[1,2,4]triazol-3-yl]-2-methyl-phenoxymethyl}-thieno[3,2-c]pyridine-7-carboxylic acid ethyl ester (85 mg; 0.151 mmol) (from Example 58 supra) with trifluoroacetic acid (1.0 mL; 13 mmol), anisole (100 μL; 0.92 mmol) (Aldrich) and sulfuric acid (50 μL; 0.94 mmol) was stirred at room temperature for 42 hours. The mixture was concentrated. The residue was diluted with dichloromethane and concentrated again. The residue was then diluted with dichloromethane and methanol and washed with saturated aqueous sodium bicarbonate solution and water. The aqueous phases were backwashed with a mixture of dichloromethane and methanol. The two organic phases were combined, dried over sodium sulfate and concentrated. The crude material was purified by flash chromatography (12 g column; EtOAc followed by a gradient to 60:40 EtOAc: methanol) to give 4-chloro-3-[2-methyl-5-(methyl-4H-[1,2,4]triazol-3-yl)-phenoxymethyl]-thieno[3,2-c]pyridine-7-carboxylic acid ethyl ester. (Yield 56.3 mg, 84.20%).

Workup

  1. concentrationThe mixture was concentrated
  2. additionThe residue was diluted with dichloromethane
  3. concentrationconcentrated again
  4. additionThe residue was then diluted with dichloromethane and methanol
  5. washwashed with saturated aqueous sodium bicarbonate solution and water
  6. additionThe aqueous phases were backwashed with a mixture of dichloromethane and methanol
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customThe crude material was purified by flash chromatography (12 g column

Sources & evidence

ORD record
ord-0909accc8b494ada9b812aebff38ffb3
Source dataset
uspto-grants-2011_04
Patent number
US07932390B2

Reaction notes

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