Dichloromethane → HCID 86732568, compound

HRID 711418Notes

Reaction equation

HRID 711418 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[F:7][C:8]([F:20])([F:19])[O:9][C:10]1[CH:11]=[C:12](B(O)O)[CH:13]=[CH:14][CH:15]=1.ClCCl.[CH3:24][O:25][C:26]1[CH:56]=[C:55]([O:57][CH3:58])[CH:54]=[CH:53][C:27]=1[CH2:28][N:29]1[CH2:34][CH:33]([CH:35]2[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH2:36]2)[N:32]2[CH:48]=[C:49](I)[CH:50]=[C:31]2[C:30]1=[O:52]>O1CCOCC1.O>[CH3:24][O:25][C:26]1[CH:56]=[C:55]([O:57][CH3:58])[CH:54]=[CH:53][C:27]=1[CH2:28][N:29]1[CH2:34][CH:33]([CH:35]2[CH2:36][CH2:37][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:39][CH2:40]2)[N:32]2[CH:48]=[C:49]([C:12]3[CH:13]=[CH:14][CH:15]=[C:10]([O:9][C:8]([F:20])([F:19])[F:7])[CH:11]=3)[CH:50]=[C:31]2[C:30]1=[O:52]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 27343853-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 86732569HCID 86732569, compound

Product 1

HCID 86732568HCID 86732568, compoundYield 32%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Cesium carbonate (32.6 mg, 0.1 mmol), [3-(trifluoromethoxy)phenyl]boronic acid (20 mg, 0.1 mmol), and 1,1′-bis(diphenylphosphino)ferrocenepaladium (4 mg, 0.005 mmol) complex with dichloromethane, were subsequently added to a solution of tert-butyl 4-[2-(2,4-dimethoxybenzyl)-7-iodo-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-4-yl]piperidine-1 carboxylate (30 mg, 0.05 mmol) in 3 ml of 1,4-dioxane and 1 ml of water, under argon atmosphere. The mixture was heated at 90° for 4 hours in a sealed vial. The reaction was filtered through a celite pad and the solvent evaporated to dryness. The crude was portioned between ethyl acetate and water, the organic layer dried over sodium sulphate and the solvent removed in vacuo. Purification by flash chromatography on silica gel column (Hex/EtOAc 8/2) afforded the compound tert-butyl 4-{2-(2,4-dimethoxybenzyl)-1-oxo-7-[3-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-4-yl}piperidine-1-carboxylate as oil (10 mg, 32%).

Workup

  1. temperatureThe mixture was heated at 90° for 4 hours in a sealed vial
  2. filtrationThe reaction was filtered through a celite pad
  3. customthe solvent evaporated to dryness
  4. dry with materialthe organic layer dried over sodium sulphate
  5. customthe solvent removed in vacuo
  6. customPurification by flash chromatography on silica gel column (Hex/EtOAc 8/2)

Sources & evidence

ORD record
ord-eeb67c76175047d39c0276be1f58f22b
Source dataset
uspto-grants-2015_11
Patent number
US09181258B2

Reaction notes

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