Water → Ammonium Hydroxide

HRID 1773903Notes

Reaction equation

HRID 1773903 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([O:8][CH:9]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[CH2:16][CH2:15][N:14]3[C:10]2=[N:11][C:12]([C:23]2[CH:28]=[CH:27][C:26]([CH2:29][CH2:30][OH:31])=[CH:25][CH:24]=2)=[CH:13]3)[CH2:4][CH2:3]1.[C:32]([N:36]=[C:37]=[O:38])([CH3:35])([CH3:34])[CH3:33].O.[OH-].[Na+]>CN(C=O)C.Cl[Cu]>[NH4+:2].[OH-:8].[CH3:1][N:2]1[CH2:3][CH2:4][CH:5]([O:8][CH:9]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[CH2:16][CH2:15][N:14]3[C:10]2=[N:11][C:12]([C:23]2[CH:24]=[CH:25][C:26]([CH2:29][CH2:30][O:31][C:37](=[O:38])[NH:36][C:32]([CH3:35])([CH3:34])[CH3:33])=[CH:27][CH:28]=2)=[CH:13]3)[CH2:6][CH2:7]1

Participants

8

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 62412tert-Butyl isocyanateHCID 86703981HCID 86703981, compound

Product 2

HCID 14923Ammonium HydroxideHCID 86703980HCID 86703980, compound

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 2-{4-[4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenyl}-ethanol (example 192) (53 mg, 0.127 mmole) in DMF (1 mL) are added tertbutylisocyanate (16 mg, 0.26 mmole) and CuCl (13 mg, 0.13 mmole). The reaction mixture is heated at 50° C. for 24 hours. Water is added, and 1N NaOH to reach pH 9-10. The aqueous phase is extracted three times with AcOEt, and the organic phase is washed with water, brine, dried over MgSO4, filtered and the solvent is removed under reduced pressure. The residue is purified by silica gel chromatography eluting with (CH2Cl2:MeOH) with a gradient from (98:2) to (9:1) then (CH2Cl2:MeOH:NH4OH) (9:9:1) to give tert-butyl-carbamic acid 2-{4-[4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenyl}-ethyl ester.

Workup

  1. extractionThe aqueous phase is extracted three times with AcOEt
  2. washthe organic phase is washed with water, brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customthe solvent is removed under reduced pressure
  6. customThe residue is purified by silica gel chromatography
  7. washeluting with (CH2Cl2:MeOH) with a gradient from (98:2) to (9:1)

Sources & evidence

ORD record
ord-430d20a20e774fe882e0d41fa9807166
Source dataset
uspto-grants-2016_02
Patent number
US09255101B2

Reaction notes

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