Water → 1-[2-(4-Cyclopropylmethylpiperazin-1-yl)phenyl]-3,3,5,5-tetramethylcyclohexanol

HRID 32270

反応式

HRID 32270 の反応式
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH:15]2[CH2:17][CH2:16]2)[CH2:10][CH2:9]1.C([Li])CCC.[CH3:23][C:24]1([CH3:33])[CH2:29][C:28]([CH3:31])([CH3:30])[CH2:27][C:26](=[O:32])[CH2:25]1.O>O1CCCC1.C(OCC)(=O)C>[CH:15]1([CH2:14][N:11]2[CH2:12][CH2:13][N:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[C:26]3([OH:32])[CH2:25][C:24]([CH3:23])([CH3:33])[CH2:29][C:28]([CH3:31])([CH3:30])[CH2:27]3)[CH2:9][CH2:10]2)[CH2:17][CH2:16]1

参加物

7

反応物 4

HCID 962WaterHCID 843993,3,5,5-TetramethylcyclohexanoneHCID 231428391-(2-Bromophenyl)-4-cyclopropylmethylpiperazineHCID 178418339Butyllithium

生成物 1

HCID 113032171-[2-(4-Cyclopropylmethylpiperazin-1-yl)phenyl]-3,3,5,5-tetramethylcyclohexanol収率 87.1%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of 1-(2-bromophenyl)-4-cyclopropylmethylpiperazine (700 mg, 2.37 mmol) produced in Example (108a) in anhydrous tetrahydrofuran (7 mL) was added dropwise n-butyllithium (1.60 M solution in hexane, 1.63 mL, 2.61 mmol) over a period of 3 minutes at an external temperature of −70° C. After stirring for 45 minutes under the same conditions, 3,3,5,5-tetramethylcyclohexanone (0.49 mL, 2.85 mmol) was added dropwise to the reaction mixture over a period of 4 minutes at an external temperature of −70° C. Stirring was continued for 15 minutes under the same conditions, and then for 18 hours and 30 minutes while warming until the external temperature reached room temperature. Water was added to the reaction mixture and extraction was performed with ethyl acetate. The separated organic layer was washed with brine and then dried over anhydrous sodium sulfate. The desiccant was filtered off and the filtrate was concentrated under reduced pressure. The resultant residue was purified by silica gel column chromatography (ethyl acetate/heptane) to give 765 mg of the title compound as a light yellow oil.

後処理

  1. additionwas added dropwise to the reaction mixture over a period of 4 minutes at an external temperature of −70° C
  2. waitfor 18 hours
  3. temperature30 minutes while warming until the external temperature
  4. customreached room temperature
  5. washThe separated organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationThe desiccant was filtered off
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe resultant residue was purified by silica gel column chromatography (ethyl acetate/heptane)

出典と根拠

ORDレコード
ord-a2d3364cb9754b3db575067c3b9b3f39
出典データセット
uspto-grants-2008_09
特許番号
US07425554B2

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