4-[(1-Benzyl-pyrrolidine-3-carbonyl)-methyl-amino]-piperidine-1-carboxylic acid tert-butyl ester → HCID 68891896, 화합물

HRID 1296389노트

반응식

HRID 1296389 반응식
[CH2:1]([Mg]Br)[CH3:2].[C:5]([O:9][C:10]([N:12]1[CH2:17][CH2:16][CH:15]([N:18]([C:20]([CH:22]2[CH2:26][CH2:25][N:24]([CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:23]2)=O)[CH3:19])[CH2:14][CH2:13]1)=[O:11])([CH3:8])([CH3:7])[CH3:6]>C1COCC1.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[C:5]([O:9][C:10]([N:12]1[CH2:17][CH2:16][CH:15]([N:18]([C:20]2([CH:22]3[CH2:26][CH2:25][N:24]([CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[CH2:23]3)[CH2:2][CH2:1]2)[CH3:19])[CH2:14][CH2:13]1)=[O:11])([CH3:8])([CH3:7])[CH3:6]

참가 물질

5

반응물 2

HCID 694925584-[(1-Benzyl-pyrrolidine-3-carbonyl)-methyl-amino]-piperidine-1-carboxylic acid tert-butyl esterHCID 178418443HCID 178418443, 화합물2회

생성물 1

HCID 68891896HCID 68891896, 화합물수율 38%

시약·촉매·용매 2

HCID 11026Titanium isopropoxide촉매2회HCID 8028Tetrahydrofuran용매4회

실험 절차

The solution of ethylmagnesium bromide (3.0 M in ethyl ether, 2.1 mL, 6.3 mmol) in THF (17.0 mL) was cooled to −78° C. To this solution was added the solution of titanium (IV) isopropoxide (0.76 mL, 2.6 mmol) in THF (1.7 mL) dropwise with the temperature below −70° C. After stirred for three minutes, the solution of 4-[(1-benzyl-pyrrolidine-3-carbonyl)-methyl-amino]-piperidine-1-carboxylic acid tert-butyl ester (1.0 g, 2.5 mmol) in THF (1.7 mL) was added. The resulting solution was warmed to room temperature, heated at reflux for one hour and then cooled to 8° C. Ethylmagnesium bromide (3.0M in ethyl ether, 1.8 mL, 5.4 mmol) was added followed by the solution of titanium (IV) isopropoxide (0.66 mL, 2.2 mmol) in THF (1.0 mL) rapidly. The reaction mixture was stirred at room temperature for one hour and partitioned between ethyl acetate and water. The separated organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative thin layer chromatography (60% ethyl acetate in hexane with 0.5% triethylamine) to give pale yellow oil (390 mg, 38%). ESI MS m/z 414.3 (M+H+).

후처리

  1. temperatureheated
  2. temperatureat reflux for one hour
  3. temperaturecooled to 8° C
  4. stirringThe reaction mixture was stirred at room temperature for one hour
  5. custompartitioned between ethyl acetate and water
  6. washThe separated organic layer was washed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by preparative thin layer chromatography (60% ethyl acetate in hexane with 0.5% triethylamine)

출처 및 근거

ORD 기록
ord-586eca18e3794382aac50b26f665b8fd
출처 데이터셋
uspto-grants-2007_07
특허 번호
US07247634B2

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