4-Toluenesulfonyl chloride → HCID 178483172, compound

HRID 1410376Notes

Reaction equation

HRID 1410376 reaction equation
[C:1]1([CH:7]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:8][N:9]([CH3:20])[C:10](=[O:19])[CH:11](O)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[NH2:40][CH2:41][CH2:42][C:43]1[N:47]=[CH:46][NH:45][CH:44]=1>O1CCCC1.CO>[C:1]1([CH:7]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:8][N:9]([CH3:20])[C:10](=[O:19])[CH:11]([NH:40][CH2:41][CH2:42][C:43]2[N:47]=[CH:46][NH:45][CH:44]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 24758Sodium hydrideHCID 22174856HCID 22174856, compoundHCID 178419017HCID 178419017, compound

Product 1

HCID 178483172HCID 178483172, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To stirred solution of the product of step 1 (1.50 g, 4.34 mmol) in tetrahydrofuran (15 mL) was added a 60% dispersion of sodium hydride in mineral oil (0.210 g, 5.25 mmol). After gas evolution ceased, p-toluenesulfonyl chloride (0.990 g, 5.20 mmol) was added and the mixture was stirred for 2 hours. At this time, histamine (1.93 g, 17.4 mmol) was added followed by methanol (10 mL). The reaction was stirred overnight and concentrated. The residue was partitioned between ethyl acetate and aqueous sodium carbonate solution. The organic layer was dried (sodium sulfate) and concentrated to afford a pasty white solid. Flash chromatography over silica (methylene chloride/methanolic ammonia solution) provided 1.08 g (57%) of product as a colorless tacky foam: 1H NMR (CDCl3) δ 7.52-7.43 (m, 1H), 7.40-7.00 (m, 15H), 6.78-6.69 (m, 1H), 4.36-3.97 (m, 4H), 2.92-2.20 (m, 7H) ppm.

Workup

  1. stirringThe reaction was stirred overnight
  2. concentrationconcentrated
  3. customThe residue was partitioned between ethyl acetate and aqueous sodium carbonate solution
  4. dry with materialThe organic layer was dried (sodium sulfate)
  5. concentrationconcentrated
  6. customto afford a pasty white solid

Sources & evidence

ORD record
ord-d0d3b79c1ea74e61b0ad63327034b964
Source dataset
uspto-grants-2014_12
Patent number
US08921547B2

Reaction notes

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