Ethanol → [2-(4-Ethoxycarbonyl-4-methylpiperidin-1-yl)pyrimidin-5-yl]boronic acid

HRID 626933

反応式

HRID 626933 の反応式
Cl[C:2]1[N:7]=[CH:6][C:5]([B:8]([OH:10])[OH:9])=[CH:4][N:3]=1.Cl.[CH3:12][C:13]1([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.C(O)C.C(N(CC)CC)C>CO.ClCCl.ClCCl>[CH2:22]([O:21][C:19]([C:13]1([CH3:12])[CH2:18][CH2:17][N:16]([C:2]2[N:7]=[CH:6][C:5]([B:8]([OH:10])[OH:9])=[CH:4][N:3]=2)[CH2:15][CH2:14]1)=[O:20])[CH3:23]

参加物

7

反応物 4

HCID 702EthanolHCID 8471TriethylamineHCID 19361804Ethyl 4-methylpiperidine-4-carboxylate hydrochlorideHCID 21747362(2-Chloropyrimidin-5-yl)boronic acid

生成物 1

HCID 89923723[2-(4-Ethoxycarbonyl-4-methylpiperidin-1-yl)pyrimidin-5-yl]boronic acid収率 61%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 21226129Dichloromethane methanol溶媒

反応条件

温度
80 °C

実験手順

To 2-chloropyrimidine-5-boronic acid (4.00 g, 25.3 mmol) were added ethyl 4-methylpiperidine-4-carboxylate hydrochloride (4.09 g, 23.9 mmol), ethanol (40 mL) and triethylamine (9.0 mL, 64.0 mmol). The mixture was heated at 80° C. for 3 h before being concentrated in vacuo. The reaction mixture was partitioned between water (100 mL) and ethyl acetate (100 mL), then the aqueous layer was separated and extracted with ethyl acetate (2×100 mL). The organic layers were combined and washed with brine (100 mL), then dried (Na2SO4). The solvent was then removed under reduced pressure and the crude reaction mixture was purified by flash column chromatography on silica (Biotage SNAP 100 g, Isolera). Gradient elution, with 100% dichloromethane to 30% methanol/dichloromethane, afforded the title compound (4.27 g, 43% yield, 74% purity) as a brown oil. LCMS (pH 10): MH+ m/z 294.1, RT 0.652 minutes.

後処理

  1. concentrationbefore being concentrated in vacuo
  2. customThe reaction mixture was partitioned between water (100 mL) and ethyl acetate (100 mL)
  3. customthe aqueous layer was separated
  4. extractionextracted with ethyl acetate (2×100 mL)
  5. washwashed with brine (100 mL)
  6. dry with materialdried (Na2SO4)
  7. customThe solvent was then removed under reduced pressure
  8. customthe crude reaction mixture
  9. customwas purified by flash column chromatography on silica (Biotage SNAP 100 g, Isolera)
  10. washGradient elution

出典と根拠

ORDレコード
ord-c481efd5e3b44959ac351b257e6d3236
出典データセット
uspto-grants-2016_04
特許番号
US09309243B2

関連ノート

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