Acetic Acid → HCID 178484114, compound

HRID 1269814Notes

Reaction equation

HRID 1269814 reaction equation
[C:1](O)(=O)C.[NH:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C@H:15]3[CH2:20][CH2:19][C@H:18](N)[CH2:17][CH2:16]3)=[CH:11][CH:12]=2)[CH:7]=[N:6]1.C=O.[C:24]([BH3-])#[N:25].[Na+].[OH-].[Na+].[ClH:30].C(OCC)C>CO>[ClH:30].[NH:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C@H:15]3[CH2:20][CH2:19][C@H:18]([N:25]([CH3:24])[CH3:1])[CH2:17][CH2:16]3)=[CH:11][CH:12]=2)[CH:7]=[N:6]1

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 10953452Ether hydrochlorideHCID 178511699HCID 178511699, compound

Product 1

HCID 178484114HCID 178484114, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Acetic acid (0.05 ml, 0.87 mmol) was added to a solution of the trans-4-(1H-indazol-5-yloxy)cyclohexanamine (0.044 g, 0.19 mmol) obtained in Example 384 and paraformaldehyde (0.040 g, 1.33 mmol) in methanol (4 ml), and the resulting mixture was stirred for 15 minutes and then ice-cooled. Sodium cyanoborohydride (0.055 g, 0.87 mmol) was added thereto and the resulting mixture was slowly warmed up to room temperature and stirred overnight. After a 1N-aqueous sodium hydroxide solution was added thereto, the solvent was distilled off under reduced pressure and the residue was dried up and then purified by a silica gel chromatography (eluent: chloroform/methanol/30%-aqueous ammonia=300/10/3). A solution of the purified residue in ethyl acetate was prepared, followed by adding thereto a 1N-hydrochloric acid-diethyl ether solution (0.5 ml). The solid precipitated was subjected to decantation with ethyl acetate (three times) and then dried up to obtain trans-4-(1H-indazol-5-yloxy)-N,N-dimethylcyclohexanamine monohydrochloride (0.0400 g, 86%).

Workup

  1. temperatureice-cooled
  2. stirringstirred overnight
  3. distillationthe solvent was distilled off under reduced pressure
  4. customthe residue was dried up
  5. custompurified by a silica gel chromatography (eluent: chloroform/methanol/30%-aqueous ammonia=300/10/3)
  6. customA solution of the purified residue in ethyl acetate was prepared
  7. additionby adding
  8. customThe solid precipitated
  9. customdried up

Sources & evidence

ORD record
ord-635b7b80c8e3470eab563865116beb36
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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