Cesium carbonate → tert-butyl 4-{3-[(3R)-3-({(1S)-3-methoxy-1-[3-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)phenyl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylat

HRID 526366Notes

Reaction equation

HRID 526366 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][C:16]([N:18]2[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24](=[O:39])[NH:25][C@H:26]([C:32]3[CH:33]=N[CH:35]=[C:36]([OH:38])[CH:37]=3)[CH2:27][C:28]([O:30][CH3:31])=[O:29])[CH2:19]2)=[O:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:40](=O)([O-])[O-].[Cs+].[Cs+].[C:46]1([CH3:69])[CH:51]=[CH:50][C:49]([S:52]([O:55][CH2:56][CH2:57]OS(C2C=CC(C)=CC=2)(=O)=O)(=[O:54])=[O:53])=[CH:48][CH:47]=1>CN(C)C=O>[CH3:31][O:30][C:28](=[O:29])[CH2:27][C@H:26]([NH:25][C:24]([C@@H:20]1[CH2:21][CH2:22][CH2:23][N:18]([C:16](=[O:17])[CH2:15][CH2:14][CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:13][CH2:12]2)[CH2:19]1)=[O:39])[C:32]1[CH:33]=[CH:40][CH:35]=[C:36]([O:38][CH2:57][CH2:56][O:55][S:52]([C:49]2[CH:48]=[CH:47][C:46]([CH3:69])=[CH:51][CH:50]=2)(=[O:53])=[O:54])[CH:37]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 228289Ethylene glycol ditosylateHCID 71259055tert-butyl-4-{3-[(3R)-3-{[(1S)-1-(5-hydroxypyridin-3-yl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

Product 1

HCID 89407759tert-butyl 4-{3-[(3R)-3-({(1S)-3-methoxy-1-[3-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)phenyl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylatYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Tert-butyl-4-{3-[(3R)-3-{[(1S)-1-(5-hydroxypyridin-3-yl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate (example 4e, 80 mg, 0.15 mmol) was dissolved in N,N-dimethylformamide (20 mL). Cesium carbonate (120 mg, 0.37 mmol) and ethylene glycol bis-p-toluenesulfonate (81 mg, 0.22 mmol) were added. The mixture was stirred at room temperature for 2 hours, quenched by addition of saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The combined extracts were washed with brine and dried over sodium sulfate. The solution was concentrated under reduced pressure and the residue was purified by preparative thin layer chromatography on silica gel (ethyl acetate in dichloromethane 60%) to yield 67 mg of tert-butyl 4-{3-[(3R)-3-({(1S)-3-methoxy-1-[3-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)phenyl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylat.

Workup

  1. customquenched by addition of saturated aqueous ammonium chloride solution
  2. extractionextracted with ethyl acetate
  3. washThe combined extracts were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationThe solution was concentrated under reduced pressure
  6. customthe residue was purified by preparative thin layer chromatography on silica gel (ethyl acetate in dichloromethane 60%)

Sources & evidence

ORD record
ord-39ad40d0561c44d6b627ac9577d03aed
Source dataset
uspto-grants-2016_05
Patent number
US09345793B2

Reaction notes

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