4-Toluenesulfonyl chloride → HCID 58833631, compound

HRID 540890Notes

Reaction equation

HRID 540890 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][C:5]1[N:6]([CH2:32][CH2:33][CH3:34])[C:7]2[C:16]3[CH:15]=[CH:14][C:13]([O:17][CH:18]4[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]4)=[CH:12][C:11]=3[N:10]=[CH:9][C:8]=2[N:31]=1.C1C=C(Cl)C=C(C(OO)=O)C=1.[OH-].[NH4+:47].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>C(Cl)(Cl)Cl>[NH2:47][C:9]1[C:8]2[N:31]=[C:5]([CH2:4][CH2:3][O:2][CH3:1])[N:6]([CH2:32][CH2:33][CH3:34])[C:7]=2[C:16]2[CH:15]=[CH:14][C:13]([O:17][CH:18]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:25])[CH2:20][CH2:19]3)=[CH:12][C:11]=2[N:10]=1

Participants

6

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 14923Ammonium HydroxideHCID 70297m-Chloroperbenzoic acidHCID 68972752HCID 68972752, compound

Product 1

HCID 58833631HCID 58833631, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A stirred solution of tert-butyl 4-{[2-(2-methoxyethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-7-yl]oxy}piperidine-1-carboxylate (9.77 g, 20.8 mmol) in chloroform (175 mL) at room temperature was treated with mCPBA (55% pure, 6.54 g, 20.8 mmol). After 45 minutes, concentrated ammonium hydroxide (175 mL) was added, followed by p-toluenesulfonyl chloride (3.97 g, 20.8 mmol). The mixture was stirred for 62 hours, then the layers were separated and the aqueous layer was extracted with chloroform. The combined organic layers were washed with water and saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The crude product was purified by flash chromatography (silica gel, gradient elution with 1.5-12.5% CMA in chloroform) followed by recrystallization from acetonitrile to afford 6.3 g of tert-butyl 4-{[4-amino-2-(2-methoxyethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-7-yl]oxy}piperidine-1-carboxylate as tan crystals, mp 173-175° C.

Workup

  1. customthe layers were separated
  2. extractionthe aqueous layer was extracted with chloroform
  3. washThe combined organic layers were washed with water and saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe crude product was purified by flash chromatography (silica gel, gradient elution with 1.5-12.5% CMA in chloroform)
  8. customfollowed by recrystallization from acetonitrile

Sources & evidence

ORD record
ord-d8b1429c4bd346dbb0dd09f397537df4
Source dataset
uspto-grants-2014_10
Patent number
US08871782B2

Reaction notes

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