Acetic Acid → tert-Butyl [5-(4-chlorophenyl)-6-methyl-2-oxopiperidin-3-yl]carbamate

HRID 448227ノート

反応式

HRID 448227 の反応式
[C:1]([O:5][C:6]([NH:8][CH:9]([CH2:14][CH:15]([C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=1)[C:16](=O)[CH3:17])[C:10](OC)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])(=O)C.[NH4+].C(O)(=O)C.C([BH3-])#[N:36].[Na+].C(=O)(O)[O-].[Na+].C(=O)([O-])[O-].[K+].[K+]>CO.O.C(O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]1[CH2:14][CH:15]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)[CH:16]([CH3:17])[NH:36][C:10]1=[O:11])([CH3:4])([CH3:3])[CH3:2]

参加物

10

反応物 6

HCID 176Acetic AcidHCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydrideHCID 68747752Methyl 2-[(tert-butoxycarbonyl)amino]-4-(4-chlorophenyl)-5-oxohexanoate

生成物 1

HCID 86665200tert-Butyl [5-(4-chlorophenyl)-6-methyl-2-oxopiperidin-3-yl]carbamate

試薬・触媒・溶媒 3

HCID 702Ethanol溶媒HCID 887Methanol溶媒HCID 962Water溶媒2 回

反応条件

温度
60 °C

実験手順

To a solution of methyl 2-[(tert-butoxycarbonyl)amino]-4-(4-chlorophenyl)-5-oxohexanoate (21.6 g, 58.4 mmol) in methanol (200 mL) were added ammonium acetate (45.0 g, 584 mmol), acetic acid (50.2 mL, 876 mmol), and sodium cyanoborohydride (5.51 g, 87.7 mmol). The mixture was heated at 60° C. for a total of 4 h. The mixture was then allowed to cool to ambient temperature and sodium bicarbonate and water were added. The mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. Ethanol (240 mL) and potassium carbonate (40.4 g, 292 mmol) were added. The mixture was stirred 1.5 h at 60° C. to effect epimerization to the desired epimer. Water was added followed by extraction with ethyl acetate (3×). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% dichloromethane→90% dichloromethane/methanol with 0.1% ammonium hydroxide) gave the title compound as a mixture of isomers. MS: m/z=361.2 (M+Na).

後処理

  1. temperatureto cool to ambient temperature
  2. extractionThe mixture was extracted with ethyl acetate (3×)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. extractionfollowed by extraction with ethyl acetate (3×)
  8. washThe combined organic extracts were washed with brine
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification by silica gel chromatography (100% dichloromethane→90% dichloromethane/methanol with 0.1% ammonium hydroxide)

出典と根拠

ORDレコード
ord-f59a692deb384689a8230f7c393b790b
出典データセット
uspto-grants-2013_07
特許番号
US08481556B2

反応ノート

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