Hydrochloric Acid → 2-(4-Cyclopropyl-phenyl)-2,8-diaza-spiro[4.5]decan-1-one

HRID 1942215ノート

反応式

HRID 1942215 の反応式
C(O[C:4]([C:6]1([CH2:19][CH2:20]OC)[CH2:11][CH2:10][N:9](C(OC(C)(C)C)=O)[CH2:8][CH2:7]1)=[O:5])C.[CH:23]1([C:26]2[CH:32]=[CH:31][C:29]([NH2:30])=[CH:28][CH:27]=2)[CH2:25][CH2:24]1.[Cl-].C[Al+]C.Cl>C1(C)C=CC=CC=1>[CH:23]1([C:26]2[CH:32]=[CH:31][C:29]([N:30]3[CH2:20][CH2:19][C:6]4([CH2:7][CH2:8][NH:9][CH2:10][CH2:11]4)[C:4]3=[O:5])=[CH:28][CH:27]=2)[CH2:25][CH2:24]1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 122539274-CyclopropylanilineHCID 16686359Dimethylalumanylium chlorideHCID 582872614-(2-Methoxy-ethyl)-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester

生成物 1

HCID 582872772-(4-Cyclopropyl-phenyl)-2,8-diaza-spiro[4.5]decan-1-one

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
115 °C

実験手順

A mixture of 1.3 g (4.1 mmol) 4-(2-Methoxy-ethyl)-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester, 0.604 g (4.5 mmol) 4-cyclopropylaniline and 8.24 mL (8.24 mmol) dimethylaluminum chloride (1N in hexane) in 100 mL toluene was stirred at 115° C. for 15 h. After cooling to room temperature the mixture was poured into ice, the mixture was acidified with HCl aq. to pH=2 and extracted with ethyl acetate. The aqueous layer was basified with NaOH pellets to pH=8 and extracted with DCM. The combined organic layers were dried with MgSO4 and evaporated to dryness. The residue was purified by column chromatography on silica (amine) with a gradient formed from ethyl acetate and methanol to yield after evaporation of the product containing fractions 0.468 g (42%) of the title compound as light yellow solid. MS m/e: 270.0 [M+H]+.

後処理

  1. temperatureAfter cooling to room temperature the mixture
  2. additionwas poured into ice
  3. extractionextracted with ethyl acetate
  4. extractionextracted with DCM
  5. dry with materialThe combined organic layers were dried with MgSO4
  6. customevaporated to dryness
  7. customThe residue was purified by column chromatography on silica (amine) with a gradient
  8. customformed from ethyl acetate and methanol
  9. customto yield
  10. customafter evaporation of the product
  11. additioncontaining fractions 0.468 g (42%) of the title compound as light yellow solid

出典と根拠

ORDレコード
ord-f0b6a5a0714b42829f5416cad43f52cd
出典データセット
uspto-grants-2013_03
特許番号
US08389539B2

反応ノート

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