Water → HCID 178441705, compound

HRID 222530

Reaction equation

HRID 222530 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:7]([C:11]1[N:12]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[C:33]3[N:37](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:36]=[N:35][N:34]=3)=[CH:23][CH:22]=2)[C:13]([C:17]([OH:19])=[O:18])=[C:14]([Cl:16])[N:15]=1)[CH2:8][CH2:9][CH3:10].[C:57](=[O:75])([O:62][C@H:63]1[CH2:67][O:66][C@@H:65]2[C@H:68]([O:71][N+:72]([O-:74])=[O:73])[CH2:69][O:70][C@H:64]12)[O:58][C@@H:59](Cl)[CH3:60].O>CN(C)C=O.CO>[CH2:7]([C:11]1[N:12]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[C:33]3[NH:37][N:36]=[N:35][N:34]=3)=[CH:23][CH:22]=2)[C:13]([C:17]([O:19][C@@H:59]([O:58][C:57]([O:62][C@H:63]2[CH2:67][O:66][C@@H:65]3[C@H:68]([O:71][N+:72]([O-:74])=[O:73])[CH2:69][O:70][C@H:64]23)=[O:75])[CH3:60])=[O:18])=[C:14]([Cl:16])[N:15]=1)[CH2:8][CH2:9][CH3:10]

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 467832052-Butyl-4-chloro-1-({2'-[1-(triphenylmethyl)-1H-tetrazol-5-yl][1,1'-biphenyl]-4-yl}methyl)-1H-imidazole-5-carboxylic acid2×HCID 58192759(1S)-1-chloroethyl (3S,3aR,6R,6aS)-6-(nitrooxy)hexahydrofuro[3,2-b]furan-3-yl carbonate2×

Product 1

HCID 178441705HCID 178441705, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

Cesium carbonate (5.34 g, 16.4 mmol) was added to a solution of 2-butyl-4-chloro-1-{[2′-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazole-5-carboxylic acid (Intermediate 4, 8.56 g, 12.6 mmol) and (1S)-1-chloroethyl (3S,3aR,6R,6aS)-6-(nitrooxy)hexahydrofuro[3,2-b]furan-3-yl carbonate (Intermediate 2, 3.75 g, 12.6 mmol) in N,N-dimethylformamide (126 mL). The mixture was heated to 70° C. for 2 hours. Water was added and the solution was extracted with ethyl acetate (2×). The combined organic layers were dried (magnesium sulfate), filtered, and concentrated in vacuo. The residue was purified by flash chromatography, eluting with 0-100% ethyl acetate in hexanes to give a yellow foam that was subsequently dissolved in methanol (106 mL). The solution was stirred at 70° C. for 2 hours and then concentrated in vacuo. The residue was purified by HPLC reverse phase (C-18), eluting with acetonitrile/water+0.1% trifluoroacetic acid to give the title compound. 1H NMR (500 MHz, CDCl3) δ 8.00 (d, J=7.5 Hz, 1H), 7.61 (t, J=7.5 Hz, 1H), 7.54 (t, J=7.5 Hz, 1H), 7.43 (d, J=8.0 Hz, 1H), 7.15 (d, J=8.0 Hz, 2H), 6.95 (d, J=8.0 Hz, 2H), 6.85 (q, J=5.5 Hz, 1H), 5.55 (d, J=16.5 Hz, 1H), 5.45 (d, J=16.5 Hz, 1H), 5.27 (td, J=5.5, 3.0 Hz, 1H), 5.03 (d, J=3.0 Hz, 1H), 4.84 (t, J=5.5 Hz, 1H), 4.39 (d, J=5.5 Hz, 1H), 4.00 (d, J=11.0 Hz, 1H), 3.95-3.88 (m, 2H), 3.78 (dd, J=11.0, 5.5 Hz, 1H), 2.66 (t, J=8.0 Hz, 2H), 1.68 (quintet, J=8.0 Hz, 2H), 1.60 (d, J=5.5 Hz, 3H), 1.36 (sextet, J=8.0 Hz, 2H), 0.89 (t, J=8.0 Hz, 3H); LC-MS: m/z 698.2 (M+H).

Workup

  1. extractionthe solution was extracted with ethyl acetate (2×)
  2. dry with materialThe combined organic layers were dried (magnesium sulfate)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography
  6. washeluting with 0-100% ethyl acetate in hexanes
  7. customto give a yellow foam that
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by HPLC reverse phase (C-18)
  10. washeluting with acetonitrile/water+0.1% trifluoroacetic acid

Sources & evidence

ORD record
ord-12a3184c410748ad9702df6356ba9f08
Source dataset
uspto-grants-2012_06
Patent number
US08207208B2

Linked notes

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