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

HRID 1292849노트

반응식

HRID 1292849 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

A stirred 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 a solution of titanium (IV) isopropoxide (0.76 mL, 2.6 mmol) in THF (1.7 mL) dropwise with the temperature below −70° C. After stiring 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 slowly warmed to room temperature, heated at reflux for one hour and then cooled to 8° C. Ethylmagnesium bromide (3.0 M in ethyl ether, 1.8 mL, 5.4 mmol) was added followed by a 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. custompartitioned between ethyl acetate and water
  5. washThe separated organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by preparative thin layer chromatography (60% ethyl acetate in hexane with 0.5% triethylamine)

출처 및 근거

ORD 기록
ord-310f4710747943d38d23474462f465ed
출처 데이터셋
uspto-grants-2007_07
특허 번호
US07238694B2

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