Cesium carbonate → tert-butyl 4-{3-[(3R)-3-{[3-methoxy-1-{5-[2-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)phenyl]pyridin-3-yl}-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

HRID 526384Notes

Reaction equation

HRID 526384 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:9]=[C:10]([CH:14]([NH:20][C:21]([C@@H:23]2[CH2:28][CH2:27][CH2:26][N:25]([C:29](=[O:45])[CH2:30][CH2:31][CH:32]3[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH2:33]3)[CH2:24]2)=[O:22])[CH2:15][C:16]([O:18][CH3:19])=[O:17])[CH:11]=[N:12][CH:13]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:52]1([CH3:75])[CH:57]=[CH:56][C:55]([S:58]([O:61][CH2:62][CH2:63]OS(C2C=CC(C)=CC=2)(=O)=O)(=[O:60])=[O:59])=[CH:54][CH:53]=1>CN(C)C=O>[CH3:19][O:18][C:16](=[O:17])[CH2:15][CH:14]([NH:20][C:21]([C@@H:23]1[CH2:28][CH2:27][CH2:26][N:25]([C:29](=[O:45])[CH2:30][CH2:31][CH:32]2[CH2:33][CH2:34][N:35]([C:38]([O:40][C:41]([CH3:42])([CH3:44])[CH3:43])=[O:39])[CH2:36][CH2:37]2)[CH2:24]1)=[O:22])[C:10]1[CH:11]=[N:12][CH:13]=[C:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[O:1][CH2:63][CH2:62][O:61][S:58]([C:55]2[CH:56]=[CH:57][C:52]([CH3:75])=[CH:53][CH:54]=2)(=[O:60])=[O:59])[CH:9]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 228289Ethylene glycol ditosylateHCID 71259040tert-butyl 4-{3-[(3R)-3-({1-[5-(2-hydroxyphenyl)pyridin-3-yl]-3-methoxy-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

Product 1

HCID 89407744tert-butyl 4-{3-[(3R)-3-{[3-methoxy-1-{5-[2-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)phenyl]pyridin-3-yl}-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylateYield 39.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

108.0 mg (0.17 mmol) Tert-butyl 4-{3-[(3R)-3-({1-[5-(2-hydroxyphenyl)pyridin-3-yl]-3-methoxy-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate (example 8d) were dissolved in 6.7 ml N,N-dimethylformamide. 170 mg (0.52 mmol) cesium carbonate and 96.4 mg (0.26 mmol) ethylene glycol bis-p-toluenesulfonate were added. The mixture was stirred at room temperature for 68 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. Chromatography over 10 g silica gel (dichloromethane/ethanol 100/0-90/10) gave 55 mg (37%) tert-butyl 4-{3-[(3R)-3-{[3-methoxy-1-{5-[2-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)phenyl]pyridin-3-yl}-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

Sources & evidence

ORD record
ord-67daeb4230734801b98cc068d3148398
Source dataset
uspto-grants-2016_05
Patent number
US09345793B2

Reaction notes

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