p-Toluenesulfonic acid monohydrate → HCID 68615352, compound

HRID 1817895Notes

Reaction equation

HRID 1817895 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH:15][CH2:16][C:17]2([OH:22])[CH2:21][CH2:20][CH2:19][CH2:18]2)=[C:6]([NH:8][C:9](=O)[C:10]([CH3:13])([CH3:12])[CH3:11])[CH:7]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:15]([CH2:16][C:17]3([OH:22])[CH2:21][CH2:20][CH2:19][CH2:18]3)[C:9]([C:10]([CH3:13])([CH3:12])[CH3:11])=[N:8][C:6]=2[CH:7]=1

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrate2×HCID 68614758HCID 68614758, compound

Product 1

HCID 68615352HCID 68615352, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of N-(5-bromo-2-{[(1-hydroxycyclopentyl)methyl]amino}phenyl)-2,2-dimethylpropanamide (Step A, 1.3 g, 3.41 mmol) in toluene (100 mL) was added p-toluenesulfonic acid monohydrate (130 mg, 0.68 mmol) at room temperature and the mixture was stirred at 140° C. for 23 h. After cooling to room temperature, p-toluenesulfonic acid monohydrate (130 mg, 0.68 mmol) was added, and the mixture was heated at 140° C. After stirring for 26 h at 140° C., the mixture was quenched with saturated sodium hydrogencarbonate aqueous solution. The mixture was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate:dichloromethane=5.5:1:0.5 as eluent) to afford the title compound (453 mg, 38%) as a beige amorphous solid.

Workup

  1. temperatureAfter cooling to room temperature
  2. temperaturethe mixture was heated at 140° C
  3. stirringAfter stirring for 26 h at 140° C.
  4. customthe mixture was quenched with saturated sodium hydrogencarbonate aqueous solution
  5. extractionThe mixture was extracted with ethyl acetate
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography on silica gel (hexane:ethyl acetate:dichloromethane=5.5:1:0.5 as eluent)

Sources & evidence

ORD record
ord-fbc784654f204e13b387641a88d2f9a2
Source dataset
uspto-grants-2009_10
Patent number
US07598393B2

Reaction notes

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