Ammonia → Ammonium Hydroxide

HRID 1773884Notes

Reaction equation

HRID 1773884 reaction equation
Br[C:2]1[C:15]2[CH2:14][CH2:13][N:12]3[C:8](=[N:9][C:10](I)=[CH:11]3)[CH:7]([O:17][CH:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[C:6]=2[CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[C:31]1(B(O)O)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.N>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[NH4+:9].[OH-:17].[CH3:24][N:21]1[CH2:20][CH2:19][CH:18]([O:17][CH:7]2[C:6]3[CH:5]=[CH:4][CH:3]=[C:2]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[C:15]=3[CH2:14][CH2:13][N:12]3[C:8]2=[N:9][C:10]([C:2]2[CH:15]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:11]3)[CH2:23][CH2:22]1

Participants

9

Reactant 4

HCID 222AmmoniaHCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 72694982HCID 72694982, compound

Product 2

HCID 14923Ammonium HydroxideHCID 72694468HCID 72694468, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 8-bromo-2-iodo-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 79A) (82 mg, 0.163 mmole) in THF (2 mL) in a screw-capped vial under argon are added 1M solution of K2CO3 (0.8 ml, 0.4 mmole), PdCl2(dppf)2 (8.2 mg) and benzeneboronic acid (26 mg, 0.21 mmole). The reaction mixture is heated at 100° C. overnight. Water is added to the reaction mixture and pH adjusted to 9-10 by adding concentrated ammonia solution. The aqueous phase is extracted three times with CH2Cl2. The organic phase is dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure. The residue is pre-purified by silica gel chromatography using (CH2Cl2:MeOH) (100:0) to (90:10) then (CH2Cl2:MeOH:NH4OH) (9:1:0.1) to give 4-(1-methylpiperidin-4-yloxy)-2,8-diphenyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene.

Workup

  1. extractionThe aqueous phase is extracted three times with CH2Cl2
  2. dry with materialThe organic phase is dried over magnesium sulphate
  3. filtrationfiltered
  4. customthe solvent is removed under reduced pressure
  5. customThe residue is pre-purified by silica gel chromatography

Sources & evidence

ORD record
ord-3da57878ccff404bb378899d10572f27
Source dataset
uspto-grants-2016_02
Patent number
US09255101B2

Reaction notes

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