Benzyl Alcohol → Benzyl 2-(5-(2,3-dichlorophenyl)pyridin-3-yl)cyclopropylcarbamate

HRID 2407461Notes

Reaction equation

HRID 2407461 reaction equation
[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[C:11]([CH:15]2[CH2:17][CH:16]2C(OC)=O)[CH:12]=[N:13][CH:14]=1.[OH-].[Na+].C1(OP(N=[N+]=[N-])([O:33][C:34]2C=CC=CC=2)=O)C=CC=CC=1.C([N:45](CC)CC)C.[CH2:50]([OH:57])[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1.C([O-])(O)=O.[Na+]>CO>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[C:11]([CH:15]2[CH2:17][CH:16]2[NH:45][C:34](=[O:33])[O:57][CH2:50][C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[CH:12]=[N:13][CH:14]=1

Participants

8

Reactant 6

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 123414Diphenylphosphoryl azideHCID 516892Sodium BicarbonateHCID 59578384Methyl 2-(5-(2,3-dichlorophenyl)pyridin-3-yl)cyclopropanecarboxylate

Product 1

HCID 59578428Benzyl 2-(5-(2,3-dichlorophenyl)pyridin-3-yl)cyclopropylcarbamateYield 27.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of methyl 2-(5-(2,3-dichlorophenyl)pyridin-3-yl)cyclopropanecarboxylate (270 mg, 0.838 mmol) in MeOH (3 ml) was added NaOH (5 M in water, 0.503 ml, 2.51 mmol) at room temperature. The resulting mixture was stirred at room temperature for 30 min. The reaction was quenched by the addition of HCl (5 M in water), and the mixture was extracted with AcOEt/trifluoroethanol (10:1). The extract was washed with water and brine, dried over Na2SO4, filtered and concentrated in vacuo. The resulting crude was dissolved in toluene (7 ml). Diphenylphosphonoazide (0.272 ml, 1.257 mmol), triethylamine (0.175 ml, 1.257 mmol) were added to the solution, which was stirred for 12 h at 100° C. Benzyl alcohol (0.523 ml, 5.03 mmol) was added to the reaction mixture and this mixture was stirred for additional 4 h. A saturated NaHCO3 solution was added at room temperature and the mixture was extracted with AcOEt. The extract was washed with water and brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash column (EtOAc/Heptane=0-50%, v/v) gave benzyl 2-(5-(2,3-dichlorophenyl)pyridin-3-yl)cyclopropylcarbamate (94.1 mg, 0.228 mmol, 27% yield) ESI-MS m/z: 413[M+1]+. 1H NMR (CDCl3, 400 MHz) ppm 1.27-1.33 (m, 2H), 2.15-2.28 (m, 1H), 2.81-2.87 (m, 1H), 5.13 (s, 2H), 7.21 (bs, 1H), 7.29 (t, J=8.0 Hz, 1H), 7.35 (s, 5H), 7.52 (dd, J=8.0, 0.6 Hz, 2H), 8.48 (s, 2H)

Workup

  1. customThe reaction was quenched by the addition of HCl (5 M in water)
  2. extractionthe mixture was extracted with AcOEt/trifluoroethanol (10:1)
  3. washThe extract was washed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe resulting crude was dissolved in toluene (7 ml)
  8. stirringwas stirred for 12 h at 100° C
  9. stirringthis mixture was stirred for additional 4 h
  10. extractionthe mixture was extracted with AcOEt
  11. washThe extract was washed with water and brine
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customPurification by flash column (EtOAc/Heptane=0-50%, v/v)

Sources & evidence

ORD record
ord-4de66618ff6b42ed8cd55b49b7b3c9cb
Source dataset
uspto-grants-2014_08
Patent number
US08809545B2

Reaction notes

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