Methanol → Cyclopropyl-[4-((S)-2-methyl-piperazin-1-yl)-piperidin-1-yl]-methanone

HRID 1500514Notes

Reaction equation

HRID 1500514 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][NH:11][C@@H:10]([CH3:14])[CH2:9]1)=O)(C)(C)C.[CH:15]1([C:18]([N:20]2[CH2:25][CH2:24][C:23](=O)[CH2:22][CH2:21]2)=[O:19])[CH2:17][CH2:16]1.CO.C([BH3-])#N.[Na+]>FC(F)(F)C(O)=O>[CH:15]1([C:18]([N:20]2[CH2:25][CH2:24][CH:23]([N:11]3[CH2:12][CH2:13][NH:8][CH2:9][C@@H:10]3[CH3:14])[CH2:22][CH2:21]2)=[O:19])[CH2:16][CH2:17]1

Participants

6

Reactant 4

HCID 887MethanolHCID 5003444Sodium cyanoborohydrideHCID 7023035(S)-1-Boc-3-methylpiperazineHCID 149949681-(Cyclopropanecarbonyl)piperidin-4-one

Product 1

HCID 86700507Cyclopropyl-[4-((S)-2-methyl-piperazin-1-yl)-piperidin-1-yl]-methanoneYield 141.4%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidCatalyst

Procedure

To a mixture of (S)-3-methyl-piperazine-1-carboxylic acid tert-butyl ester (220 mg, 1.1 mmol) and 1-(cyclopropylcarbonyl)piperidin-4-one (150 mg, 0.9 mmol) in methanol (5 mL, 120 mmol) was added slowly trifluoroacetic acid (6.9 μL, 0.09 mmol) followed by sodium cyanoborohydride (56 mg, 0.9 mmol). The reaction mixture was stirred overnight at RT, concentrated by rotary evaporation, washed with 1 N NaOH (20 mL) and extracted with EtOAc (3×15 mL). Combined organic fractions were washed with brine, dried with sodium sulfate, and concentrated by rotary evaporation to afford a white solid (320 mg). A mixture of the white solid in 4 M HCl in 1,4-dioxane (5 mL) was stirred at RT for 30 min and concentrated to provide the di-HCl salt of the title intermediate (180 mg, 62% yield) as a white suspension.

Workup

  1. concentrationconcentrated by rotary evaporation
  2. washwashed with 1 N NaOH (20 mL)
  3. extractionextracted with EtOAc (3×15 mL)
  4. washCombined organic fractions were washed with brine
  5. dry with materialdried with sodium sulfate
  6. concentrationconcentrated by rotary evaporation

Sources & evidence

ORD record
ord-77cfb4ec9869432ca8eb6cbf828ca6f8
Source dataset
uspto-grants-2015_12
Patent number
US09206159B2

Reaction notes

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