Sodium Hydroxide → HCID 178464530, compound

HRID 1269816Notes

Reaction equation

HRID 1269816 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([O:10][C@H:11]3[CH2:16][CH2:15][C@H:14]([NH:17][C:18](=O)[CH3:19])[CH2:13][CH2:12]3)=[CH:7][CH:8]=2)[CH:3]=[N:2]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+].[ClH:29].C(OCC)C>O1CCCC1.O>[ClH:29].[CH2:18]([NH:17][C@H:14]1[CH2:13][CH2:12][C@H:11]([O:10][C:6]2[CH:5]=[C:4]3[C:9](=[CH:8][CH:7]=2)[NH:1][N:2]=[CH:3]3)[CH2:16][CH2:15]1)[CH3:19]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 10953452Ether hydrochlorideHCID 21226445Aluminium lithium hydrideHCID 178475035HCID 178475035, compound

Product 1

HCID 178464530HCID 178464530, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

The trans-N-[4-(1H-indazol-5-yloxy)cyclohexyl]acetamide (0.066 g, 0.24 mmol) obtained in Example 391 was added to a suspension of lithium aluminum hydride (0.040 g, 1.05 mmol) in tetrahydrofuran (5 ml) and stirred for 12 hours with heating under reflux. The resulting solution was cooled on an ice bath, followed by adding dropwise thereto water (0.05 ml), a 2N-aqueous sodium hydroxide solution (0.10 ml) and water (0.15 ml) in that order. Thereafter, the insoluble material was removed by filtration using Celite. The filtrate was purified by a silica gel chromatography (eluent: chloroform/methanol/30%-aqueous ammonia=10/1/0 to 100/10/1). A solution of the purified material in ethyl acetate was prepared and a 1N-hydrochloric acid/diethyl ether solution (0.5 ml) was added thereto. The solid precipitated was subjected to decantation with ethyl acetate and dried up to obtain trans-N-ethyl-4-(1H-indazol-5-yloxy)cyclohexanamine monohydrochloride (0.057 g, 80%).

Workup

  1. temperaturewith heating
  2. temperatureunder reflux
  3. temperatureThe resulting solution was cooled on an ice bath
  4. additionby adding dropwise
  5. customThereafter, the insoluble material was removed by filtration
  6. customThe filtrate was purified by a silica gel chromatography (eluent: chloroform/methanol/30%-aqueous ammonia=10/1/0 to 100/10/1)
  7. customA solution of the purified material in ethyl acetate was prepared
  8. customThe solid precipitated
  9. customdried up

Sources & evidence

ORD record
ord-c438213fd5224db980a62bbdbc874f47
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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