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 1858077Notes

Reaction equation

HRID 1858077 reaction equation
[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]

Participants

8

Reactant 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

Product 1

HCID 1363337192-{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 esterYield 206.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-ce3c47d03074446b84d6d473b4d2013d
Source dataset
uspto-grants-2000_11
Patent number
US06150352

Reaction notes

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