Cesium carbonate → HCID 86641746, compound

HRID 1798476Notes

Reaction equation

HRID 1798476 reaction equation
[CH:1]1([N:4]([CH2:39][C:40]2[CH:45]=[C:44]([CH2:46][CH2:47][CH2:48][O:49][CH3:50])[CH:43]=[C:42]([OH:51])[CH:41]=2)[C:5]([C@@H:7]2[C@@H:12]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][O:22][C:23]4[C:28]([Cl:29])=[CH:27][C:26]([CH3:30])=[CH:25][C:24]=4[Cl:31])=[CH:15][CH:14]=3)[CH2:11][CH2:10][N:9]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:8]2)=[O:6])[CH2:3][CH2:2]1.Br[CH2:53][CH2:54][CH2:55][C:56]#[N:57].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.CCOC(C)=O>[C:56]([CH2:55][CH2:54][CH2:53][O:51][C:42]1[CH:41]=[C:40]([CH:45]=[C:44]([CH2:46][CH2:47][CH2:48][O:49][CH3:50])[CH:43]=1)[CH2:39][N:4]([CH:1]1[CH2:3][CH2:2]1)[C:5]([C@@H:7]1[C@@H:12]([C:13]2[CH:14]=[CH:15][C:16]([O:19][CH2:20][CH2:21][O:22][C:23]3[C:28]([Cl:29])=[CH:27][C:26]([CH3:30])=[CH:25][C:24]=3[Cl:31])=[CH:17][CH:18]=2)[CH2:11][CH2:10][N:9]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:8]1)=[O:6])#[N:57]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 214124-BromobutyronitrileHCID 68492454tert-Butyl (3R,4S)-3-({cyclopropyl[3-hydroxy-5-(3-methoxypropyl)benzyl]-amino}carbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}piperidine-1-carboxylate

Product 1

HCID 86641746HCID 86641746, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl (3R,4S)-3-({cyclopropyl[3-hydroxy-5-(3-methoxy-propyl)benzyl]amino}carbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]-phenyl}piperidine-1-carboxylate (1 eq.) from Example 1/Step 2 in DMF (0.2 M) was added 4-bromobutanenitrile (1.2 eq.) and cesium carbonate (1.3 eq.). The reaction was stirred at rt for 18 h, then heated to 65° C. for 4 h. After cooling to rt, the reaction was diluted with EtOAc. The aqueous layer was extracted with EtOAc. The combined organic extracts were washed with saturated aqueous NH4Cl solution, 5% aqueous HCl, saturated aqueous NaHCO3 solution, and brine. The organic solution was dried over MgSO4 and concentrated in vacuo to afford the title compound as an oil.

Workup

  1. temperatureheated to 65° C. for 4 h
  2. temperatureAfter cooling to rt
  3. extractionThe aqueous layer was extracted with EtOAc
  4. washThe combined organic extracts were washed with saturated aqueous NH4Cl solution, 5% aqueous HCl, saturated aqueous NaHCO3 solution, and brine
  5. dry with materialThe organic solution was dried over MgSO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a43d9c467a4341be9f31bc76bce485ae
Source dataset
uspto-grants-2013_01
Patent number
US08343968B2

Reaction notes

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