1,2-Diaminocyclohexane, trans- → HCID 71145478, compound

HRID 535334Notes

Reaction equation

HRID 535334 reaction equation
[O-]P([O-])([O-])=O.[K+].[K+].[K+].[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([C@H:16]2[C:25]3[C:20](=[CH:21][C:22]([O:30][CH3:31])=[C:23]([O:26][CH:27]([CH3:29])[CH3:28])[CH:24]=3)[CH2:19][C:18](=[O:32])[NH:17]2)=[CH:12][CH:11]=1.Br[C:34]1[CH:39]=[CH:38][C:37]([C:40]([C:43]23[CH2:50][CH2:49][CH:46]([CH2:47][CH2:48]2)[O:45][CH2:44]3)([OH:42])[CH3:41])=[CH:36][CH:35]=1.N[C@@H]1CCCC[C@H]1N>O1CCOCC1.[Cu]I>[Cl:9][C:10]1[CH:11]=[CH:12][C:13]([C@H:16]2[C:25]3[C:20](=[CH:21][C:22]([O:30][CH3:31])=[C:23]([O:26][CH:27]([CH3:28])[CH3:29])[CH:24]=3)[CH2:19][C:18](=[O:32])[N:17]2[C:34]2[CH:35]=[CH:36][C:37]([C:40]([OH:42])([C:43]34[CH2:48][CH2:47][CH:46]([CH2:49][CH2:50]3)[O:45][CH2:44]4)[CH3:41])=[CH:38][CH:39]=2)=[CH:14][CH:15]=1

Participants

7

Reactant 4

HCID 438061,2-Diaminocyclohexane, trans-HCID 62657Potassium Phosphate, TribasicHCID 58437804HCID 58437804, compoundHCID 71145822HCID 71145822, compound

Product 1

HCID 71145478HCID 71145478, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent2×

Procedure

A dry microwave vial was charged with K3PO4 (255 mg, 1.203 mmol), (S)-1-(4-chlorophenyl)-7-isopropoxy-6-methoxy-1,2-dihydroisoquinolin-3(4H)-one (208 mg, 0.601 mmol), 1-(4-bromo-phenyl)-1-(2-oxa-bicyclo[2.2.2]oct-4-yl)ethanol (225 mg, 0.722 mmol) and dioxane (1.9 ml). The reaction mixture was degassed with argon, then trans-1,2-diaminocyclohexane (69 mg, 0.072 ml, 0.601 mmol) and copper(I)iodide (115 mg, 0.601 mmol) were added. The vial was sealed and heated for 17 hrs to 97° C. in an oil bath. The reaction mixture was diluted with dioxane, filtered through a pad of hyflo, the residue was washed with dioxane and the filtrate concentrated to dryness. The crude product was purified by silica gel column chromatography (eluting with a gradient of DCM:DCM/EtOH (9/1) 95:05 to 50:50) yielding the title example (223 mg, 0.387 mmol, 64%) as a beige resin.

Workup

  1. customThe reaction mixture was degassed with argon
  2. customThe vial was sealed
  3. temperatureheated for 17 hrs to 97° C. in an oil bath
  4. filtrationfiltered through a pad of hyflo
  5. washthe residue was washed with dioxane
  6. concentrationthe filtrate concentrated to dryness
  7. customThe crude product was purified by silica gel column chromatography (
  8. washeluting with a gradient of DCM
  9. customDCM/EtOH (9/1) 95:05 to 50:50) yielding the title example (223 mg, 0.387 mmol, 64%) as a beige resin

Sources & evidence

ORD record
ord-980552f6844a45dc99b5d01217b19617
Source dataset
uspto-grants-2014_10
Patent number
US08859535B2

Reaction notes

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