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

HRID 1500514ノート

反応式

HRID 1500514 の反応式
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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6422Trifluoroacetic acid触媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-77cfb4ec9869432ca8eb6cbf828ca6f8
出典データセット
uspto-grants-2015_12
特許番号
US09206159B2

反応ノート

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