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Triphosgene → 2-{2-[7-Chloro-3-(3,5-dimethylphenyl)-2-oxo-6-(5-oxo-4,5-dihydro-tetrazol-1-yl)-1,2-dihydro-quinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid 2-trimethylsilanylethyl ester

HRID 1858077
ノート
印刷プレビュー

反応式

HRID 1858077 の反応式
[CH3:1][Si:2]([CH3:39])([CH3:38])[CH2:3][CH2:4][O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][CH2:15][O:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([Cl:28])=[C:24]([NH2:27])[CH:25]=2)[NH:20][C:19](=[O:29])[C:18]=1[C:30]1[CH:35]=[C:34]([CH3:36])[CH:33]=[C:32]([CH3:37])[CH:31]=1)=[O:7].ClC(Cl)(O[C:44](=[O:50])OC(Cl)(Cl)Cl)Cl.[N-:52]=[N+:53]=[N-:54].[Al+3].[N-]=[N+]=[N-].[N-]=[N+]=[N-].C([O-])(=O)C(C(C([O-])=O)O)O.[K+].[K+]>C(Cl)Cl.O.N1C=CC=CC=1>[CH3:39][Si:2]([CH3:38])([CH3:1])[CH2:3][CH2:4][O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][CH2:15][O:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([Cl:28])=[C:24]([N:27]3[C:44](=[O:50])[NH:54][N:53]=[N:52]3)[CH:25]=2)[NH:20][C:19](=[O:29])[C:18]=1[C:30]1[CH:35]=[C:34]([CH3:36])[CH:33]=[C:32]([CH3:37])[CH:31]=1)=[O:7]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 94429TriphosgeneHCID 6100505Dipotassium 2,3-dihydroxybutanedioateHCID 21652180Aluminum azideHCID 545003552-{2-[6-Amino-7-chloro-3-(3,5-dimethylphenyl)-2-oxo-1,2-dihydroquinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid 2-trimethylsilanylethyl ester

生成物 1

HCID 136333719
2-{2-[7-Chloro-3-(3,5-dimethylphenyl)-2-oxo-6-(5-oxo-4,5-dihydro-tetrazol-1-yl)-1,2-dihydro-quinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid 2-trimethylsilanylethyl ester
収率 206.3%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 1049Pyridine溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

To a solution of 2-{2-[6-amino-7-chloro-3-(3,5-dimethylphenyl)-2-oxo-1,2-dihydroquinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid 2-trimethylsilanylethyl ester (173 mg in 5 mL dry methylene chloride) at 0° C. was added triphosgene (36 mg) followed by 0.073 mL of pyridine and the mixture stirred for 2 hour at 0° C. At this time the reaction was quenched by the addition water, washed with brine, dried over sodium sulfate and concentrated in vacuo to give the crude isocyante. This was solvated in 2 mL methylene chloride and added by cannula to a freshly prepared solution of aluminum azide (0.6 mmols in 5 mL tetrahydrofuran) and the resulting mixture heated to reflux on an oil bath. After 20 hours, the mixture was added to 10 mL of an iced, 1M potassium tartarate solution and stirred for 20 minutes. This was then diluted with water and extracted with ethyl acetate. The organic portion was washed successively with 1 M potassium tartarate, saturated ammonium chloride, water and brine, then dried over sodium sulfate. Purification of the concentrate by flash chromatography on silica gel (chloroform:10% acetic acid in methanol, 97:3) gave the title compound (160 mg).

後処理

  1. customAt this time the reaction was quenched by the addition water
  2. washwashed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customto give the crude isocyante
  6. temperaturethe resulting mixture heated
  7. temperatureto reflux on an oil bath
  8. waitAfter 20 hours
  9. stirringstirred for 20 minutes
  10. extractionextracted with ethyl acetate
  11. washThe organic portion was washed successively with 1 M potassium tartarate, saturated ammonium chloride, water and brine
  12. dry with materialdried over sodium sulfate
  13. customPurification of the
  14. concentrationconcentrate by flash chromatography on silica gel (chloroform:10% acetic acid in methanol, 97:3)

出典と根拠

ORDレコード
ord-ce3c47d03074446b84d6d473b4d2013d
出典データセット
uspto-grants-2000_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06150352

反応ノート

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