Methanol → 1-[(4,4-Difluorocyclohexyl)methyl]piperidin-4-amine

HRID 446001Notes

Reaction equation

HRID 446001 reaction equation
Cl.O1CCOCC1.[F:8][C:9]1([F:30])[CH2:14][CH2:13][CH:12]([CH2:15][N:16]2[CH2:21][CH2:20][CH:19]([NH:22]C(=O)OC(C)(C)C)[CH2:18][CH2:17]2)[CH2:11][CH2:10]1.CO.[OH-].[Na+]>C(OCC)(=O)C>[F:30][C:9]1([F:8])[CH2:10][CH2:11][CH:12]([CH2:15][N:16]2[CH2:17][CH2:18][CH:19]([NH2:22])[CH2:20][CH2:21]2)[CH2:13][CH2:14]1

Participants

6

Reactant 4

HCID 887MethanolHCID 14798Sodium HydroxideHCID 204431481,4-Dioxane hydrochlorideHCID 71293727tert-Butyl N-{1-[(4,4-difluorocyclohexyl)methyl]piperidin-4-yl}carbamate

Product 1

HCID 712936341-[(4,4-Difluorocyclohexyl)methyl]piperidin-4-amineYield 92%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A 4 N hydrogen chloride/1,4-dioxane solution (11 ml, 43 mmol) was added to a mixture of tert-butyl N-{1-[(4,4-difluorocyclohexyl)methyl]piperidin-4-yl}carbamate obtained in Example 2c (650 mg, 1.96 mmol) and methanol (11 ml), followed by stirring at room temperature for three hours. After concentrating the reaction liquid, the residue was dissolved in ethyl acetate, a 1N aqueous sodium hydroxide solution was added, and the organic layer was separated. The aqueous layer was further extracted with ethyl acetate twice, the organic layers were dried over sodium sulfate, and the solvent was then distilled off to give the title compound (419 mg, yield 92%).

Workup

  1. concentrationAfter concentrating
  2. customthe reaction liquid
  3. customthe organic layer was separated
  4. extractionThe aqueous layer was further extracted with ethyl acetate twice
  5. dry with materialthe organic layers were dried over sodium sulfate
  6. distillationthe solvent was then distilled off

Sources & evidence

ORD record
ord-79f32c68ea7c499c888d14bc18a225e5
Source dataset
uspto-grants-2013_07
Patent number
US08476301B2

Reaction notes

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