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

HRID 446000Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 446000
[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

Komponenten

6

Edukt 4

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

Produkt 1

HCID 71293727tert-Butyl N-{1-[(4,4-difluorocyclohexyl)methyl]piperidin-4-yl}carbamateAusbeute 20,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 57417360Sodium chloride; waterLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

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%).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-cd0a90cf4ca241a3b0e09a915b73937d
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08476301B2

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