Potassium Iodide → 2-Cyclopropyl-3-[[2'-[2-(triphenylmethyl)-2H-tetrazol-5-yl][1,1'-biphenyl]-4-yl]oxy]-4-quinolinecarboxylic acid, 2-methyl-1-(2,2-dimethyl-1-oxopropoxy)propyl ester

HRID 1953847Notes

Reaction equation

HRID 1953847 reaction equation
C1(C2C(OC3C=CC(C4C=CC=CC=4C4N=NNN=4)=CC=3)=C(C(OC(OC(=O)CC)C(C)C)=O)C3C(=CC=CC=3)N=2)CC1.[CH:44]1([C:47]2[C:56]([O:57][C:58]3[CH:63]=[CH:62][C:61]([C:64]4[CH:69]=[CH:68][CH:67]=[CH:66][C:65]=4[C:70]4[N:71]=[N:72][N:73]([C:75]([C:88]5[CH:93]=[CH:92][CH:91]=[CH:90][CH:89]=5)([C:82]5[CH:87]=[CH:86][CH:85]=[CH:84][CH:83]=5)[C:76]5[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=5)[N:74]=4)=[CH:60][CH:59]=3)=[C:55]([C:94]([OH:96])=[O:95])[C:54]3[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=3)[N:48]=2)[CH2:46][CH2:45]1.[CH3:97][C:98]([CH3:108])([CH3:107])[C:99]([O:101][CH:102](Cl)[CH:103]([CH3:105])[CH3:104])=[O:100].C(=O)([O-])[O-].[K+].[K+].[I-].[K+].C1OCCOCCOCCOCCOCCOC1>CN(C)C=O.C(OCC)(=O)C>[CH:44]1([C:47]2[C:56]([O:57][C:58]3[CH:59]=[CH:60][C:61]([C:64]4[CH:69]=[CH:68][CH:67]=[CH:66][C:65]=4[C:70]4[N:71]=[N:72][N:73]([C:75]([C:88]5[CH:89]=[CH:90][CH:91]=[CH:92][CH:93]=5)([C:76]5[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=5)[C:82]5[CH:83]=[CH:84][CH:85]=[CH:86][CH:87]=5)[N:74]=4)=[CH:62][CH:63]=3)=[C:55]([C:94]([O:96][CH:102]([O:101][C:99](=[O:100])[C:98]([CH3:97])([CH3:108])[CH3:107])[CH:103]([CH3:105])[CH3:104])=[O:95])[C:54]3[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=3)[N:48]=2)[CH2:45][CH2:46]1

Participants

9

Reactant 6

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 2855718-Crown-6HCID 23298234HCID 23298234, compoundHCID 443050072-Cyclopropyl-3-[[2'-(2H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]oxy]-4-quinolinecarboxylic acid, 2-methyl-1-(1-oxopropoxy)propyl esterHCID 537383751-Chloro-2-methylpropyl 2,2-dimethylpropanoate

Product 1

HCID 571891962-Cyclopropyl-3-[[2'-[2-(triphenylmethyl)-2H-tetrazol-5-yl][1,1'-biphenyl]-4-yl]oxy]-4-quinolinecarboxylic acid, 2-methyl-1-(2,2-dimethyl-1-oxopropoxy)propyl esterYield 72.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of the title A compound of Example 28, 2-cyclopropyl-3-[[2'-[2-(triphenylmethyl)-2H-tetrazol-5-yl][1,1'-biphenyl]-4-yl]oxy]-4-quinolinecarboxylic acid (1.55 mmol), the title B compound of Example 16, 2,2-dimethylpropanoic acid, 1-chloro-2-methylpropyl ester (1.09 g, 6.65 mmol), potassium carbonate (521 mg, 3.77 mmol), potassium iodide (375 mg, 2.26 mmol), and 18-crown-6 (100 mg, 0.378 mmol) in dimethylformamide (3.7 mL) was heated at 90° C. for 2.5 hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (75 mL) and filtered. The organic filtrate was rinsed with aq. 5% sodium bisulfite and brine, dried (magnesium sulfate), and concentrated in vacuo to give a crude product (2 g). Flash chromatography on silica gel (60 g) eluted with 1 column volume of hexanes followed by 1.8 L of 12:1, then 900 mL of 8:1, hexanes:ethyl acetate yielded the title compound (950 mg, 72%).

Workup

  1. filtrationfiltered
  2. washThe organic filtrate was rinsed with aq. 5% sodium bisulfite and brine
  3. dry with materialdried (magnesium sulfate)
  4. concentrationconcentrated in vacuo
  5. customto give a crude product (2 g)
  6. washFlash chromatography on silica gel (60 g) eluted with 1 column volume of hexanes

Sources & evidence

ORD record
ord-0c0e8f1908234ac7844da0c51c4ec2fb
Source dataset
uspto-grants-2000_09
Patent number
US06117885

Reaction notes

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