Cesium carbonate → HCID 86641745, compound

HRID 1798474Notes

Reaction equation

HRID 1798474 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]([O:58][CH2:59][CH3:60])=[O:57].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.CCOC(C)=O>[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]([O:51][CH2:53][CH2:54][CH2:55][C:56]([O:58][CH2:59][CH3:60])=[O:57])[CH:41]=2)[C:5]([C@@H:7]2[C@@H:12]([C:13]3[CH:14]=[CH:15][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:17][CH:18]=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

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 76300Ethyl 4-bromobutyrateHCID 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 86641745HCID 86641745, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

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 ethyl 4-bromobutanoate (1.6 eq.) and cesium carbonate (1.3 eq.). The reaction was heated to 80° C. for 3 h. After cooling down to rt, the reaction was diluted with EtOAc. The organic extract was washed with water, brine, dried over MgSO4, and concentrated in vacuo. The crude product was purified by flash column chromatography (SiO2, 50% EtOAc in Hex) to afford the title compound as an oil.

Workup

  1. temperatureAfter cooling down to rt
  2. extractionThe organic extract
  3. washwas washed with water, brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash column chromatography (SiO2, 50% EtOAc in Hex)

Sources & evidence

ORD record
ord-25b212518cfd4cdcaa196d0e620b50cc
Source dataset
uspto-grants-2013_01
Patent number
US08343968B2

Reaction notes

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