Tert-Butyl nitrite → HCID 11294280, compound

HRID 1716615Notes

Reaction equation

HRID 1716615 reaction equation
N[C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1[N:21]([CH3:29])[S:22]([C:25]([F:28])([F:27])[F:26])(=[O:24])=[O:23].N(OC(C)(C)C)=O>O1CCCC1.C(#N)C.CS(C)=O.O>[C:19]([C:4]1[C:3]([N:21]([CH3:29])[S:22]([C:25]([F:28])([F:26])[F:27])(=[O:24])=[O:23])=[CH:2][N:6]([C:7]2[C:8]([Cl:18])=[CH:9][C:10]([C:14]([F:16])([F:17])[F:15])=[CH:11][C:12]=2[Cl:13])[N:5]=1)#[N:20]

Participants

7

Reactant 2

HCID 10906Tert-Butyl nitriteHCID 11518638HCID 11518638, compound

Product 1

HCID 11294280HCID 11294280, compoundYield 55.2%

Reagents, catalysts & solvents 4

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of Example 20 (150 mg, 0.31 mmol) in tetrahydrofuran (5 ml) was added dropwise tert-butyl nitrite (111 μl, 0.93 mmol). The reaction mixture was then heated at 60° C. overnight. The reaction mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate (20 ml) and water (20 ml). The organic layer was separated, washed with brine (20 ml), dried (Na2SO4) and concentrated in vacuo. The residue was purified by column chromatography (silica, 10 g) eluting with dichloromethane/ethyl acetate [9:1]. The appropriate fractions were combined and concentrated to give the crude product. The crude product was dissolved in a mixture of acetonitrile, dimethyl sulphoxide and water (4:5:1, 2 ml) and purified by automated preparative liquid chromatography (Gilson system, 150 mm×30 mm Phenomonex LUNA C18(2) 10 μm column) using an acetonitrile:water gradient [60:40 to 95:5]. The appropriate fractions were concentrated in vacuo to give the titled compound (80 mg).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue was partitioned between ethyl acetate (20 ml) and water (20 ml)
  3. customThe organic layer was separated
  4. washwashed with brine (20 ml)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (silica, 10 g)
  8. washeluting with dichloromethane/ethyl acetate [9:1]
  9. concentrationconcentrated
  10. customto give the crude product
  11. custompurified
  12. concentrationThe appropriate fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-5174c536bcf2413f88363a4730a815a8
Source dataset
uspto-grants-2010_09
Patent number
US07803832B2

Reaction notes

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