Water → HCID 178438615, compound

HRID 519807

Reaction equation

HRID 519807 reaction equation
[OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([N:8]2[C:13](=[O:14])[C:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]4[C:23]([C:28]#[N:29])=[CH:24][CH:25]=[CH:26][CH:27]=4)=[CH:18][CH:17]=3)=[C:11]([CH2:30][CH2:31][CH3:32])[N:10]3[N:33]=[CH:34][CH:35]=[C:9]23)[CH2:4][CH2:3]1.[N+](=[C:38]([CH3:44])[C:39](OCC)=O)=[N-].[C:45](OCC)(=O)[CH3:46].[OH2:51]>C(Cl)Cl.C([O-])(=O)C.[Rh+3].C([O-])(=O)C.C([O-])(=O)C>[OH:51][C:38]([CH3:39])([CH3:44])[CH:45]([CH3:46])[O:1][C@H:2]1[CH2:3][CH2:4][C@H:5]([N:8]2[C:13](=[O:14])[C:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]4[C:23]([C:28]#[N:29])=[CH:24][CH:25]=[CH:26][CH:27]=4)=[CH:18][CH:17]=3)=[C:11]([CH2:30][CH2:31][CH3:32])[N:10]3[N:33]=[CH:34][CH:35]=[C:9]23)[CH2:6][CH2:7]1

Participants

7

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 534409222-Diazonio-1-ethoxyprop-1-en-1-olateHCID 178438588HCID 178438588, compound

Product 1

HCID 178438615HCID 178438615, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 168478Rhodium acetateCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4′-{[4-(trans-4-hydroxycyclohexyl)-5-oxo-7-propyl-4,5-dihydropyrazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (0.70 g) and rhodium acetate (dimer, 0.066 g) in methylene chloride (5 mL) was added dropwise a solution of ethyl 2-diazopropanoate (1.0 g) in methylene chloride (2 mL), and the mixture was stirred for 18 hr. Ethyl acetate and water were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and then with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was crudely purified by silica gel column chromatography. This was dissolved in tetrahydrofuran (5 mL), methylmagnesium bromide (1 M tetrahydrofuran solution, 3 mL) was added dropwise at 0° C., and the mixture was stirred for 1 hr. The mixture was diluted with ethyl acetate and then saturated aqueous ammonium chloride solution was added. The mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a pale-yellow amorphous solid (0.45 g, 84%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water
  3. dry with materialwith saturated brine, dried over anhydrous magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue was crudely purified by silica gel column chromatography
  6. dissolutionThis was dissolved in tetrahydrofuran (5 mL)
  7. additionmethylmagnesium bromide (1 M tetrahydrofuran solution, 3 mL) was added dropwise at 0° C.
  8. stirringthe mixture was stirred for 1 hr
  9. additionThe mixture was diluted with ethyl acetate
  10. additionsaturated aqueous ammonium chloride solution was added
  11. extractionThe mixture was extracted with ethyl acetate
  12. washthe organic layer was washed with saturated brine
  13. dry with materialdried over anhydrous magnesium sulfate
  14. concentrationconcentrated
  15. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-d9164bc27ddf4eb0aa2ac91dff1a8865
Source dataset
uspto-grants-2015_08
Patent number
US09115136B2

Linked notes

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