Cesium carbonate → HCID 86641749, compound

HRID 1798480Notes

Reaction equation

HRID 1798480 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.C[C:53]1[CH:60]=[C:59]([CH2:61]Br)[CH:58]=[CH:57][C:54]=1[C:55]#[N:56].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.CCOCC>[C:55]([C:54]1[CH:57]=[CH:58][C:59]([CH2:61][O:51][C:42]2[CH:41]=[C:40]([CH:45]=[C:44]([CH2:46][CH2:47][CH2:48][O:49][CH3:50])[CH:43]=2)[CH2:39][N:4]([CH:1]2[CH2:3][CH2:2]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])=[CH:60][CH:53]=1)#[N:56]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 226159811001055-64-6HCID 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 86641749HCID 86641749, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of tert-butyl (3R,4 S)-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 (0.05 M) was added methyl 4-(bromomethyl)benzonitrile (1.6 eq.) and cesium carbonate (1.3 eq.). The reaction was heated to 80° C. and stirred for 16 h. After cooling to rt, the reaction was diluted with ether and quenched with water. The aqueous layer was extracted with ether. The combined organic extracts were washed with water, brine, dried over MgSO4, and concentrated in vacuo. The crude product was purified by flash column chromatography (SiO2, 5% EtOQc in Hex→100% EtOAc) to afford the title compound as a oil

Workup

  1. temperatureAfter cooling to rt
  2. customquenched with water
  3. extractionThe aqueous layer was extracted with ether
  4. washThe combined organic extracts were washed with water, brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash column chromatography (SiO2, 5% EtOQc in Hex→100% EtOAc)

Sources & evidence

ORD record
ord-e05ca5cca4574e4fb8565137f762698d
Source dataset
uspto-grants-2013_01
Patent number
US08343968B2

Reaction notes

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