Potassium Carbonate → Tradipitant

HRID 130680Notes

Reaction equation

HRID 130680 reaction equation
[N:1]([CH2:4][C:5]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[C:7]([C:15]([F:18])([F:17])[F:16])[CH:6]=1)=[N+:2]=[N-:3].C(=O)([O-])[O-].[K+].[K+].P(O)(O)(O)=O.[Cl:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[C:37]([C:39]1[C:40]([CH:45]=[C:46](O)[C:47]2[CH:52]=[CH:51][N:50]=[CH:49][CH:48]=2)=[N:41][CH:42]=[CH:43][CH:44]=1)=[O:38].[OH-].[Na+]>CS(C)=O.C(Cl)Cl>[F:18][C:15]([F:16])([F:17])[C:7]1[CH:6]=[C:5]([CH:10]=[C:9]([C:11]([F:13])([F:14])[F:12])[CH:8]=1)[CH2:4][N:1]1[C:46]([C:47]2[CH:48]=[CH:49][N:50]=[CH:51][CH:52]=2)=[C:45]([C:40]2[C:39]([C:37]([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=3[Cl:30])=[O:38])=[CH:44][CH:43]=[CH:42][N:41]=2)[N:3]=[N:2]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 441857431-(Azidomethyl)-3,5-bis(trifluoromethyl)benzeneHCID 136347866(2-Chlorophenyl)-[2-(2-hydroxy-2-pyridin-4-yl-vinyl)pyridin-3-yl]methanone phosphate

Product 1

HCID 9916461Tradipitant

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

Add 1-azidomethyl-3,5-bistrifluoromethylbenzene (3.73 g, 13.8 mmol) and potassium carbonate (5.73 g, 41.4 mmol) to a solution of (2-chlorophenyl)-[2-(2-hydroxy-2-pyridin-4-yl-vinyl)pyridin-3-yl]methanone phosphate (6.0 g, 13.8 mmol) in DMSO (16 mL). Heat to 40° C. and stir for approximately 20-24 h. Cool the reaction mixture to ambient temperature, and add the mixture to CH2Cl2 (75 mL) and 1 N NaOH (75 mL). Separate the layers, and extract the aqueous layer with CH2Cl2 (50 mL). Separate the layers, combine the organic layers and extract the combined organic layers with 1 N NaOH (2×50 mL). Add MgSO4 and acid-washed carbon (1.2 g), stir for 20 min and filter through Celite®. Concentrate the filtrate to a total weight of approximately 25 g. Add heptane (75 mL) dropwise over approximately 45 min. Seed the solution with the title compound if necessary. Stir the resulting slurry for 1 h and then filter to obtain the title compound. Dry the title compound, then add it to isopropanol (36 mL). Heat the mixture until the solid dissolves (approx. 65° C.). Allow the solution to cool to ambient temperature. Stir the resulting slurry for approximately 3 hours. Cool the slurry in an ice/water bath and stir for 2 h. Filter and dry to afford the title compound as a white solid. MS(IS) 588 (M+1). TLC (3% MeOH/CH2Cl2) Rf=0.17. 1H NMR (400 MHz, CDCl3): 5.46 (s, 2H); 7.19 (m, 5H); 7.36 (dd, 1H, J=4.9, 7.8); 7.45 (s, 2H); 7.59 (m, 1H); 7.83 (s, 1H); 7.93 (dd, 1H, J=1.5, 7.8); 8.56 (dd, 1H, J=1.5, 4.9); 8.70 (d, 2H, J=5.9).

Workup

  1. temperatureCool the reaction mixture to ambient temperature
  2. customSeparate the layers
  3. extractionextract the aqueous layer with CH2Cl2 (50 mL)
  4. customSeparate the layers
  5. extractionextract the combined organic layers with 1 N NaOH (2×50 mL)
  6. washAdd MgSO4 and acid-washed carbon (1.2 g)
  7. stirringstir for 20 min
  8. filtrationfilter through Celite®
  9. concentrationConcentrate the filtrate to a total weight of approximately 25 g
  10. waitAdd heptane (75 mL) dropwise over approximately 45 min
  11. stirringStir the resulting slurry for 1 h
  12. filtrationfilter

Sources & evidence

ORD record
ord-885c3fcd128b4768a8aeb263567579e2
Source dataset
uspto-grants-2008_06
Patent number
US07381826B2

Reaction notes

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