Cyclohexanone → N-(1-Cyclohexyl-piperidin-4-yl)-N-(4-fluoro-phenyl)-acetamide

HRID 507859Notes

Reaction equation

HRID 507859 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[C:9](=[O:11])[CH3:10])=[CH:4][CH:3]=1.[C:18]1(=O)[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl>[CH:18]1([N:15]2[CH2:16][CH2:17][CH:12]([N:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[C:9](=[O:11])[CH3:10])[CH2:13][CH2:14]2)[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1

Participants

5

Reactant 3

HCID 7967CyclohexanoneHCID 5049666Sodium triacetoxyborohydrideHCID 18539208HCID 18539208, compound

Product 1

HCID 11951208N-(1-Cyclohexyl-piperidin-4-yl)-N-(4-fluoro-phenyl)-acetamide

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

N-(4-fluoro-phenyl)-N-piperidin-4-yl-acetamide (60 mg; 0.25 mmol; 1 eq.), see Example 6 for deprotection procedure, and cyclohexanone (29 mg; 0.30 mmol; 1.2 eq.) were dissolved in DCE (2 mL). NaBH(OAc)3 (108 mg; 0.51 mmol; 2 eq.) was added, and the reaction was stirred at room temperature for 72 hours and then quenched with 1N NaOH (5 mL). DCM (5 mL) was then added and the layers were separated. The aqueous layer was washed with DCM (10 mL) and the combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude residue was purified using reversed-phase HPLC (2-99% CH3CN/H2O gradient with 0.05% TFA). LC/MS M/Z 319.2, Retention time=1.88 minutes; 10-99% CH3CN/H2O gradient with 0.05% TFA.

Workup

  1. customquenched with 1N NaOH (5 mL)
  2. additionDCM (5 mL) was then added
  3. customthe layers were separated
  4. washThe aqueous layer was washed with DCM (10 mL)
  5. dry with materialthe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude residue was purified

Sources & evidence

ORD record
ord-bb8fe3bf796a4fbd91d29254726acbee
Source dataset
uspto-grants-2010_08
Patent number
US07786308B2

Reaction notes

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