Tetrahydrofuran → tert-Butyl N-{1-[(4,4-difluorocyclohexyl)methyl]piperidin-4-yl}carbamate

HRID 446000Notes

Reaction equation

HRID 446000 reaction equation
[F:1][C:2]1([F:10])[CH2:7][CH2:6][CH:5]([CH:8]=O)[CH2:4][CH2:3]1.O1CCCC1.[NH:16]1[CH2:21][CH2:20][CH:19]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:18][CH2:17]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>[Cl-].[Na+].O>[F:1][C:2]1([F:10])[CH2:7][CH2:6][CH:5]([CH2:8][N:16]2[CH2:17][CH2:18][CH:19]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:27])([CH3:26])[CH3:28])[CH2:20][CH2:21]2)[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 7238334-(N-Boc-amino)piperidineHCID 5049666Sodium triacetoxyborohydrideHCID 113555624,4-Difluorocyclohexane-1-carbaldehyde

Product 1

HCID 71293727tert-Butyl N-{1-[(4,4-difluorocyclohexyl)methyl]piperidin-4-yl}carbamateYield 20.7%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of the crude product of 4,4-difluorocyclohexane-1-carbaldehyde obtained in Example 2b (1.4 g) and tetrahydrofuran (100 ml) was cooled to 0° C., tert-butyl N-(piperidin-4-yl)carbamate (2.27 g, 11.3 mmol) was added thereto, followed by stirring for 20 minutes. Sodium triacetoxyborohydride (2.2 g, 10.4 mmol) was then added to the reaction mixture, which was stirred at mom temperature for eight hours. Brine was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, and the solvent was distilled off. The residue was purified by silica gel column chromatography (elution solvent: ethyl acetate/heptane). The resulting residue was dissolved in ethyl acetate and washed with a saturated aqueous sodium bicarbonate solution, and the solvent was then distilled off to give the title compound (650 mg, yield 20.7%).

Workup

  1. stirringwas stirred at mom temperature for eight hours
  2. extractionwas extracted with ethyl acetate
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. distillationthe solvent was distilled off
  5. customThe residue was purified by silica gel column chromatography (elution solvent: ethyl acetate/heptane)
  6. dissolutionThe resulting residue was dissolved in ethyl acetate
  7. washwashed with a saturated aqueous sodium bicarbonate solution
  8. distillationthe solvent was then distilled off

Sources & evidence

ORD record
ord-cd0a90cf4ca241a3b0e09a915b73937d
Source dataset
uspto-grants-2013_07
Patent number
US08476301B2

Reaction notes

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