Tetrahydrofuran → Tert-butyl 4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

HRID 1525932ノート

反応式

HRID 1525932 の反応式
Cl[CH2:2][C:3]([N:5]([CH2:8][C:9]1([OH:22])[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]1)[CH2:6][CH3:7])=[O:4].O1CCCC1.[H-].[Na+].C(=O)(O)[O-].[Na+]>O.C(OCC)(=O)C>[CH2:6]([N:5]1[CH2:8][C:9]2([CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)[O:22][CH2:2][C:3]1=[O:4])[CH3:7]

参加物

7

反応物 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 86725432tert-butyl 4-((2-chloro-N-ethylacetamido)methyl)-4-hydroxypiperidine-1-carboxylate

生成物 1

HCID 71270774Tert-butyl 4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate収率 61%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a 250 mL round bottom flask containing tert-butyl 4-((2-chloro-N-ethylacetamido)methyl)-4-hydroxypiperidine-1-carboxylate (3.14 g) was added tetrahydrofuran (50 mL). The entire vessel was placed under nitrogen and stirred at room temperature. To this was portionwise added NaH (60% in mineral oil, 2 g, 50.0 mmol). After complete addition, the reaction mixture was stirred at room temperature. After 3 hours, saturated aq sodium bicarbonate (70 mL) was added to the flask (slowly dropwise via pipette at first, then the final 60 mL can be added directly). The solution was transferred to a reparatory funnel containing ethyl acetate (150 mL) and water (50 mL). The organic layer was washed with the aqueous solution, separated, and set aside. The aqueous layer was washed with ethyl acetate (1×50 mL). The combined organic extracts were washed with brine (2×50 mL), separated, dried over sodium sulfate, filtered, and concentrated in vacuo. Purification of the residue by flash chromatography (50-100% ethyl acetate:hexanes) afforded the title compound (1.7 g, 61%). MS(ES)+ m/e 299.5 [M+H]+.

後処理

  1. additionAfter complete addition
  2. stirringthe reaction mixture was stirred at room temperature
  3. additioncan be added directly)
  4. customThe solution was transferred to a reparatory funnel
  5. washThe organic layer was washed with the aqueous solution
  6. customseparated
  7. washThe aqueous layer was washed with ethyl acetate (1×50 mL)
  8. washThe combined organic extracts were washed with brine (2×50 mL)
  9. customseparated
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customPurification of the residue by flash chromatography (50-100% ethyl acetate:hexanes)

出典と根拠

ORDレコード
ord-8b207c689fef4bd7a3a2bd4be1502eb4
出典データセット
uspto-grants-2015_07
特許番号
US09084794B2

反応ノート

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