1,1'-Carbonyldiimidazole → HCID 86695396, compound

HRID 525513Notes

Reaction equation

HRID 525513 reaction equation
[Cl:1][CH:2]([Cl:23])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:20]=[CH:19][C:15]([C:16](O)=[O:17])=[CH:14][CH:13]=2)[O:7][C:6]1([CH3:22])[CH3:21])=[O:4].C(N1C=CN=C1)(N1C=CN=C1)=O.C([O-])(=O)C.[Na+].O[NH:42][C:43](=[NH:53])[CH2:44][NH:45][C:46](=[O:52])[O:47][C:48]([CH3:51])([CH3:50])[CH3:49]>CN(C)C=O.C(OC(=O)C)C.C1(C)C=CC=CC=1>[Cl:23][CH:2]([Cl:1])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:20]=[CH:19][C:15]([C:16]3[O:17][N:53]=[C:43]([CH2:44][NH:45][C:46](=[O:52])[O:47][C:48]([CH3:50])([CH3:49])[CH3:51])[N:42]=3)=[CH:14][CH:13]=2)[O:7][C:6]1([CH3:22])[CH3:21])=[O:4]

Participants

8

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 517045Sodium Acetate2×HCID 86695395HCID 86695395, compoundHCID 178453716HCID 178453716, compound

Product 1

HCID 86695396HCID 86695396, compoundYield 38.7%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the product of Step 2, Example 8 (525 mg, 1.4 mmol) in dimethylformamide (15 mL) is added 1,1′-Carbonyldiimidazole (286 mg, 1.7 mmol). The resulting solution is stirred at room temperature for 30 minutes at which time sodium acetate (140 mg, 1.7 mmol) and commercially available tert-butyl 2-(hydroxyamino)-2-iminoethylcarbamate (325 mg, 1.7 mmol) are added. The reaction is then stirred at room temperature for 72 hours. Next, the reaction is diluted with ethylacetate (75 mL) and washed with water (3×75 mL). The organic phase is dried (Na2SO4) and concentrated under vacuum. To the residue is added toluene (15 mL) and sodium acetate (140 mg, 1.7 mmol). The resulting mixture is heated to reflux for 18 hours while stirring, then cooled to room temperature and concentrated under vacuum. The residue is chromatographed on silica gel eluting from 100% hexanes to 50:50 EtOAc:hexanes to afford the title compound (280 mg): 1H NMR (400 MHz, CDCl3) 8.19 (d, 2H, J=8.0 Hz), 7.64 (d, 2H, J=8.0 Hz), 6.33 (m, 1H), 5.16 (m, 2H) 4.88-4.52 (m, 4H), 1.75 (s, 3H), 1.59 (s, 3H), 1.50 (s, 9H). m/z (Cl) 461 [M-(CH3)2CO].

Workup

  1. additionare added
  2. washwashed with water (3×75 mL)
  3. dry with materialThe organic phase is dried (Na2SO4)
  4. concentrationconcentrated under vacuum
  5. temperatureThe resulting mixture is heated
  6. temperatureto reflux for 18 hours
  7. stirringwhile stirring
  8. temperaturecooled to room temperature
  9. concentrationconcentrated under vacuum
  10. customThe residue is chromatographed on silica gel eluting from 100% hexanes to 50:50 EtOAc

Sources & evidence

ORD record
ord-d296e929d66340fba5714269c4bc7318
Source dataset
uspto-grants-2016_05
Patent number
US09340564B2

Reaction notes

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