p-Toluenesulfonic acid monohydrate → HCID 68615352, compound

HRID 643707Notes

Reaction equation

HRID 643707 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 C, 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 hydrogen carbonate 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.

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 hydrogen carbonate 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-65e5ac6b6b0a4a13a3d244dc16f0e236
Source dataset
uspto-grants-2010_04
Patent number
US07700618B2

Reaction notes

Loading…