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

HRID 526367Notes

Reaction equation

HRID 526367 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:14][C:15]([C@@H:17]2[CH2:22][CH2:21][CH2:20][N:19]([C:23](=[O:39])[CH2:24][CH2:25][CH:26]3[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]3)[CH2:18]2)=[O:16])[CH2:9][C:10]([O:12][CH3:13])=[O:11])=[CH:4][CH:3]=1.C(=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>[CH3:13][O:12][C:10](=[O:11])[CH2:9][CH:8]([NH:14][C:15]([C@@H:17]1[CH2:22][CH2:21][CH2:20][N:19]([C:23](=[O:39])[CH2:24][CH2:25][CH:26]2[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:36])([CH3:38])[CH3:37])=[O:33])[CH2:28][CH2:27]2)[CH2:18]1)=[O:16])[C:5]1[CH:6]=[CH:7][C:2]([O:1][CH2:57][CH2:56][O:55][S:52]([C:49]2[CH:50]=[CH:51][C:46]([CH3:69])=[CH:47][CH:48]=2)(=[O:54])=[O:53])=[CH:3][CH:4]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 228289Ethylene glycol ditosylateHCID 712590204-(3-{(R)-3-[1-(4-hydroxy-phenyl)-2-methoxycarbonyl-ethylcarbamoyl]-piperidin-1-yl}-3-oxo-propyl)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 71609593tert-butyl 4-{3-[(3R)-3-({3-methoxy-1-[4-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)phenyl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylateYield 70.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

100 mg (0.18 mmol) Tert-butyl 4-[3-((3R)-3-{[1-(4-hydroxyphenyl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl)-3-oxopropyl]piperidine-1-carboxylate (example 2b) were dissolved in 7 ml N,N-dimethylformamide. 179 mg (0.55 mmol) cesium carbonate and 102 mg (0.28 mmol) ethylene glycol bis-p-toluenesulfonate were added. The mixture was stirred at room temperature for 48 hours and concentrated. The remainder was taken up with saturated ammonium chloride solution and ethyl acetate. The aqueous phase was extracted with 3×20 ml ethyl acetate. The extracts were dried over sodium sulfate and concentrated to yield 195 mg. Chromatography over 5 g silica gel (dichloromethane/ethanol 100/0-95/5) gave 95 mg (63%) tert-butyl 4-{3-[(3R)-3-({3-methoxy-1-[4-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)phenyl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate.

Workup

  1. concentrationconcentrated
  2. extractionThe aqueous phase was extracted with 3×20 ml ethyl acetate
  3. dry with materialThe extracts were dried over sodium sulfate
  4. concentrationconcentrated
  5. customto yield 195 mg

Sources & evidence

ORD record
ord-22ff091cab974ad69df8f0caf11297b2
Source dataset
uspto-grants-2016_05
Patent number
US09345793B2

Reaction notes

Loading…