Ammonium Chloride → HCID 70663231, compound

HRID 878221Notes

Reaction equation

HRID 878221 reaction equation
[C:1]1([CH3:14])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:12]=[CH:11][N:10]=[CH:9][C:8]=1[NH2:13].[O:15]1[CH2:18][C:17](=O)[CH2:16]1.C([BH3-])#N.[Na+].[NH4+].[Cl-]>CO.[Cl-].[Zn+2].[Cl-].CCOC(C)=O>[O:15]1[CH2:18][CH:17]([NH:13][C:8]2[CH:9]=[N:10][CH:11]=[CH:12][C:7]=2[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=2[CH3:14])[CH2:16]1

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 5003444Sodium cyanoborohydrideHCID 150242543-Oxetanone2×HCID 69042848HCID 69042848, compound

Product 1

HCID 70663231HCID 70663231, compound

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalyst2×HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4-o-tolylpyridin-3-amine (0.125 g, 678 μmol) and oxetan-3-one (147 mg, 2.04 mmol, CAS RN 6704-31-0) in methanol (2 mL) was treated with zinc chloride (370 mg, 2.71 mmol). The reaction mixture got slightly warm and a solution formed. Then, molecular sieves 4 Å (100 mg, 678 μmol) were added and the reaction mixture refluxed for 19 hours. After cooling to room temperature another batch of oxetan-3-one (147 mg, 2.04 mmol) was added and the reaction mixture was heated again to reflux for another 24 hours before zinc chloride (185 mg, 1.36 mmol) was added. After stirring for another 2 hours sodium cyanoborohydride (128 mg, 2.04 mmol, CAS RN 25895-60-7) was added and the reaction mixture was stirred at reflux for 2 hours. After stirring at room temperature overnight, the reaction mixture was poured on saturated aqueous NH4Cl solution and EtOAc and the mixture was filtered over dicalite. The layers were separated and the aqueous layer was extracted twice with EtOAc. The organic layers were washed with brine, dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified twice by silica gel chromatography on a 10 g column using a MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). Off-white foam (0.072 g; 42%). MS (ESI): m/z=241.13 [M+H]+.

Workup

  1. temperatureThe reaction mixture got slightly warm
  2. customa solution formed
  3. additionThen, molecular sieves 4 Å (100 mg, 678 μmol) were added
  4. temperaturethe reaction mixture refluxed for 19 hours
  5. additionwas added
  6. temperaturethe reaction mixture was heated again
  7. additionwas added
  8. additionwas added
  9. temperatureat reflux for 2 hours
  10. stirringAfter stirring at room temperature overnight
  11. filtrationthe mixture was filtered over dicalite
  12. customThe layers were separated
  13. extractionthe aqueous layer was extracted twice with EtOAc
  14. washThe organic layers were washed with brine
  15. dry with materialdried over MgSO4
  16. filtrationfiltered
  17. additiontreated with silica gel
  18. customevaporated
  19. customThe compound was purified twice by silica gel chromatography on a 10 g column
  20. washeluting with a gradient of n-heptane:EtOAc (100:0 to 0:100)

Sources & evidence

ORD record
ord-8211f02752a94af1a639018650141654
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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