Hydrochloric Acid → HCID 178422431, compound

HRID 931670Notes

Reaction equation

HRID 931670 reaction equation
[H-].[Na+].[CH3:3][CH:4]([CH3:12])[C:5](=O)[CH2:6][C:7](OC)=[O:8].[Br:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20]Cl)=[C:16]([CH3:22])[CH:15]=1.Cl.O.[NH2:25][NH2:26]>O1CCCC1>[Br:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][C:6]2[C:7]([OH:8])=[N:25][NH:26][C:5]=2[CH:4]([CH3:12])[CH3:3])=[C:16]([CH3:22])[CH:15]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 24654Hydrazine hydrate (1:1)HCID 24758Sodium hydrideHCID 2759969Methyl 4-methyl-3-oxopentanoateHCID 200723584-Bromo-1-(chloromethyl)-2-methylbenzene

Product 1

HCID 178422431HCID 178422431, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
70 °C

Procedure

Add sodium hydride (8.29 g, 0.21 mol, 60% dispersion in oil) to a solution of methyl 4-methyl-3-oxovalerate (27.1 mL, 0.19 mol) in tetrahydrofuran at 0° C. After 30 min at room temperature, add a solution of 4-bromo-1-chloromethyl-2-methyl-benzene (35.0 g, 0.16 mol) in tetrahydrofuran (50 mL). Heat the resulting mixture at 70° C. overnight (18 hours). Add 1.0 M HCl (20 mL) to quench the reaction. Extract with ethyl acetate (200 mL), wash extract with water (200 mL) and brine (200 mL), dry over Na2SO4, filter and concentrate under reduced pressure. Dissolve the resulting residue in toluene (200 mL) and add hydrazine monohydrate (23.3 mL, 0.48 mol). Heat the mixture at 120° C. for 2 hours with a Dean-Stark apparatus to remove water. Cool and remove the solvent under the reduced pressure, dissolve the residue with dichloromethane (50 mL) and methanol (50 mL). Pour this solution slowly to a beaker with water (250 mL). Collect the resulting precipitated product by vacuum filtration. Dry in vacuo in an oven overnight at 40° C. to yield the title compound as a solid (48.0 g, 0.16 mol). MS (m/z): 311.0 (M+1), 309.0 (M−1).

Workup

  1. customto quench
  2. customthe reaction
  3. extractionExtract with ethyl acetate (200 mL)
  4. washwash
  5. extractionextract with water (200 mL) and brine (200 mL)
  6. dry with materialdry over Na2SO4
  7. filtrationfilter
  8. concentrationconcentrate under reduced pressure
  9. dissolutionDissolve the resulting residue in toluene (200 mL)
  10. temperatureHeat the mixture at 120° C. for 2 hours with a Dean-Stark apparatus
  11. customto remove water
  12. temperatureCool
  13. customremove the solvent under the reduced pressure
  14. dissolutiondissolve the residue with dichloromethane (50 mL) and methanol (50 mL)
  15. additionPour this solution slowly to a beaker with water (250 mL)
  16. customCollect the resulting
  17. customprecipitated product
  18. filtrationby vacuum filtration
  19. customDry in vacuo in an oven overnight at 40° C.

Sources & evidence

ORD record
ord-ebf02e6756444a0ab9fbe4f8edb502d4
Source dataset
uspto-grants-2016_03
Patent number
US09296775B2

Reaction notes

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