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

HRID 526371Notes

Reaction equation

HRID 526371 reaction equation
C(O[C:9]1[CH:10]=[C:11]([C@@H:15]([NH:21][C:22]([C@@H:24]2[CH2:29][CH2:28][CH2:27][N:26]([C:30](=[O:46])[CH2:31][CH2:32][CH:33]3[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]3)[CH2:25]2)=[O:23])[CH2:16][C:17]([O:19][CH3:20])=[O:18])[CH:12]=[N:13][CH:14]=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(C)C=CC(S([O:62][CH2:63][CH2:64][O:65][S:66]([C:69]2[CH:74]=[CH:73][C:72]([CH3:75])=[CH:71][CH:70]=2)(=[O:68])=[O:67])(=O)=O)=CC=1>CN(C)C=O>[CH3:20][O:19][C:17](=[O:18])[CH2:16][C@H:15]([NH:21][C:22]([C@@H:24]1[CH2:29][CH2:28][CH2:27][N:26]([C:30](=[O:46])[CH2:31][CH2:32][CH:33]2[CH2:34][CH2:35][N:36]([C:39]([O:41][C:42]([CH3:43])([CH3:45])[CH3:44])=[O:40])[CH2:37][CH2:38]2)[CH2:25]1)=[O:23])[C:11]1[CH:12]=[N:13][CH:14]=[C:9]([O:62][CH2:63][CH2:64][O:65][S:66]([C:69]2[CH:70]=[CH:71][C:72]([CH3:75])=[CH:73][CH:74]=2)(=[O:67])=[O:68])[CH:10]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 228289Ethylene glycol ditosylateHCID 71259024Tert-butyl 4-{3-[(3R)-3-({(1S)-1-[5-(benzyloxy)pyridin-3-yl]-3-methoxy-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

Product 1

HCID 71609635tert-butyl 4-{3-[(3R)-3-({(1S)-3-methoxy-1-[5-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)pyridin-3-yl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylatYield 39.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Tert-butyl 4-{3-[(3R)-3-({(1S)-1-[5-(benzyloxy)pyridin-3-yl]-3-methoxy-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate (example 5e, 200 mg, 0.37 mmol) was dissolved in N,N-dimethylformamide (25.3 mL). Cesium carbonate (298 mg, 0.92 mmol) and ethylene glycol bis-p-toluenesulfonate (203 mg, 0.55 mmol) were added. The mixture was stirred at room temperature for 2 hours and stored at 5° C. for 17 hours. The mixture was 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 100%) to yield 109 mg of tert-butyl 4-{3-[(3R)-3-({(1S)-3-methoxy-1-[5-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)pyridin-3-yl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylat.

Workup

  1. waitstored at 5° C. for 17 hours
  2. customThe mixture was quenched by addition of saturated aqueous ammonium chloride solution
  3. extractionextracted with ethyl acetate
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationThe solution was concentrated under reduced pressure
  7. customthe residue was purified by preparative thin layer chromatography on silica gel (ethyl acetate 100%)

Sources & evidence

ORD record
ord-20a6e253964b488281338652614098da
Source dataset
uspto-grants-2016_05
Patent number
US09345793B2

Reaction notes

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