Benzyl Alcohol → HCID 58671545, compound

HRID 2221105Notes

Reaction equation

HRID 2221105 reaction equation
[CH2:1]([N:8]1[C:13]2[N:14]=[N:15][C:16]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:17][C:12]=2[CH2:11][CH:10](C(OC(C)(C)C)=O)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:31](=[O:34])(O)[O-].[Na+].Cl.C1C=CC(P([N:51]=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.C(N(CC)CC)C.[CH2:61]([OH:68])[C:62]1[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1>C(O)(C(F)(F)F)=O.ClCCl.O1CCOCC1.CCOC(C)=O>[CH2:1]([N:8]1[C:13]2[N:14]=[N:15][C:16]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)=[CH:17][C:12]=2[CH2:11][CH:10]([NH:51][C:31](=[O:34])[O:68][CH2:61][C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

10

Reactant 6

HCID 244Benzyl AlcoholHCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 516892Sodium BicarbonateHCID 69224197HCID 69224197, compound

Product 1

HCID 58671545HCID 58671545, compoundYield 44%

Reagents, catalysts & solvents 3

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

A solution of compound 5F (0.083 g, 0.207 mmol) in 1.5 mL of 1:2 TFA/dichloromethane) was stirred at room temperature for 3 h, evaporated under reduced pressure and re-evaporated from carbon tetrachloride. The yellow oil was dissolved in ethyl acetate, washed with 10% citric acid and the aqueous layer re-extracted with EtOAc. The organic extracts were combined, dried (MgSO4) and evaporated to give a yellow semi-solid. The solid was treated with saturated sodium bicarbonate solution and then brought to pH 6 with 1 M hydrochloric acid. The aqueous phase was extracted twice with EtOAc. The extracts were combined, dried (MgSO4), filtered and evaporated to give a yellow solid. This solid was slurried in 1.0 mL of dioxane and DPPA (0.031 mL, 0.144 mmol), triethylamine (0.021 mL, 0.151 mmol) and benzyl alcohol (0.015 mL, 0.145 mmol) were added. After 20 min at room temperature, the mixture was heated to reflux for 15 h. The resulting deep red solution was cooled, diluted with EtOAc, washed once with saturated sodium bicarbonate solution, dried (MgSO4), filtered and evaporated. Purification by silica gel chromatography (7:93 Ether/CH2Cl2) provided the title compound benzyl 8-benzyl-3-phenyl-5,6,7,8-tetrahydropyrido[2,3-c]pyridazin-6-ylcarbamate as a red solid (0.024 g, 44%). MS [M+H]+: found 451.

Workup

  1. customevaporated under reduced pressure
  2. customre-evaporated from carbon tetrachloride
  3. dissolutionThe yellow oil was dissolved in ethyl acetate
  4. washwashed with 10% citric acid
  5. extractionthe aqueous layer re-extracted with EtOAc
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. customto give a yellow semi-solid
  9. extractionThe aqueous phase was extracted twice with EtOAc
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. customevaporated
  13. customto give a yellow solid
  14. temperaturethe mixture was heated
  15. temperatureto reflux for 15 h
  16. temperatureThe resulting deep red solution was cooled
  17. washwashed once with saturated sodium bicarbonate solution
  18. dry with materialdried (MgSO4)
  19. filtrationfiltered
  20. customevaporated
  21. customPurification by silica gel chromatography (7:93 Ether/CH2Cl2)

Sources & evidence

ORD record
ord-24733701987046c78f149fd3e6b0fa2f
Source dataset
uspto-grants-2008_05
Patent number
US07368458B2

Reaction notes

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