p-Toluenesulfonic acid → HCID 69085774, compound

HRID 594663Notes

Reaction equation

HRID 594663 reaction equation
[NH2:1][C:2]1[C:3]([OH:28])=[C:4]([CH:10]2[N:15]([CH2:16][C:17]3[CH:26]=[CH:25][C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[N:18]=3)[C:14](=[O:27])[CH2:13][CH2:12][CH2:11]2)[C:5]([O:8][CH3:9])=[CH:6][CH:7]=1.[CH3:29]C1C=CC(S(O)(=O)=O)=CC=1.C(OCC)(OCC)OCC>CCOC(C)=O>[CH3:9][O:8][C:5]1[CH:6]=[CH:7][C:2]2[N:1]=[CH:29][O:28][C:3]=2[C:4]=1[CH:10]1[N:15]([CH2:16][C:17]2[CH:26]=[CH:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]=2)[C:14](=[O:27])[CH2:13][CH2:12][CH2:11]1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 31214Ethyl orthoformateHCID 69081808HCID 69081808, compound

Product 1

HCID 69085774HCID 69085774, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-(3-amino-2-hydroxy-6-methoxyphenyl)-1-(quinolin-2-ylmethyl)piperidin-2-one (100 mg; 0.26 mmol; synthesis described in example 279), commercially available p-TsOH (2 mg; 0.01 mmol), and commercially available triethyl orthoformate (264 mg; 1.69 mmol) was refluxed (100° C.) for 1 h. After cooling to rt, AcOEt was added, and the obtained mixture was filtered over a pad of celite. The filtrate was then washed with water and brine, and the mixed aq. layers were further extracted with AcOEt. The mixed organic layers were then dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Subsequent purification by FC (DCM/MeOH=20/1) afforded the target compound. LC-MS (conditions A): tR=0.53 min.; [M+H]+: 388.05 g/mol.

Workup

  1. temperatureAfter cooling to rt
  2. filtrationthe obtained mixture was filtered over a pad of celite
  3. washThe filtrate was then washed with water and brine
  4. extractionthe mixed aq. layers were further extracted with AcOEt
  5. dry with materialThe mixed organic layers were then dried over anh. MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure
  8. customSubsequent purification by FC (DCM/MeOH=20/1)
  9. customafforded the target compound

Sources & evidence

ORD record
ord-e7d5996b0d25453090138fac8229441b
Source dataset
uspto-grants-2016_01
Patent number
US09242970B2

Reaction notes

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