1-Methylpiperazine → 1-[2-Hydroxy-5-(4-methylpiperazin-1-yl)phenyl]ethanone

HRID 45805

反応式

HRID 45805 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=1.[CH3:12][N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[OH:11][C:5]1[CH:4]=[CH:3][C:2]([N:16]2[CH2:17][CH2:18][N:13]([CH3:12])[CH2:14][CH2:15]2)=[CH:7][C:6]=1[C:8](=[O:10])[CH3:9]

参加物

5

反応物 2

HCID 531671-MethylpiperazineHCID 959915'-Bromo-2'-hydroxyacetophenone

生成物 1

HCID 679739361-[2-Hydroxy-5-(4-methylpiperazin-1-yl)phenyl]ethanone収率 51%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
70 °C

実験手順

1-(5-bromo-2-hydroxyphenyl)ethanone 1.0 g (4.65 mmol) in THF (10 ml), N-methylpiperazine 0.83 ml (7.45 mmol), LiHMDSA 16.2 ml (16.2 mmol), Pd2(dba)3 68 mg (0.074 mmol) and 2-dicyclohexylphosphino-2′-N,N-dimethylaminobiphenyl 29.3 mg (0.074 mmol) were combined under argon in a capped vial and stirred at 70° C. for 40 minutes. The volatiles were removed in vacuo, the obtained residue was dissolved with water and 1 N HCl (pH=6) and portioned with DCM. The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography (DCM gradient to 10% MeOH/DCM) to provide 532 mg (51%) of desired product as a brown solid. LC/MS (254 nm) HPLC method 2 Rt 3.34 min. 1H NMR (401 MHz, DMSO-d6) δ 11.45 (s, 1H), 7.21-7.28 (m, 2H), 6.80-6.93 (m, 1H), 2.98-3.10 (m, 4H), 2.63 (s, 3H), 2.44-2.48 (m, 4H), 2.23 (s, 3H). HRMS (ESI) calcd for C13H18N2O2 [M+H]+ 235.1441 Found 235.1448.

後処理

  1. customThe volatiles were removed in vacuo
  2. dissolutionthe obtained residue was dissolved with water and 1 N HCl (pH=6)
  3. washThe organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash column chromatography (DCM gradient to 10% MeOH/DCM)

出典と根拠

ORDレコード
ord-aeb794bda26b4d999630502e62d6f8b9
出典データセット
uspto-grants-2013_09
特許番号
US08541576B2

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