Ammonia → HCID 12681766, compound

HRID 543857Notes

Reaction equation

HRID 543857 reaction equation
Br[C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.O1C=CCCC1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1O[C:29]2([CH2:34][CH2:33][C:32](C#N)([N:35]([CH3:37])[CH3:36])[CH2:31][CH2:30]2)[O:28]C1.[Cl-].[NH4+].Cl.N>C(OCC)C.C(Cl)(Cl)Cl.CO.C1C=CC=CC=1.O1CCCC1>[OH:8][C:4]1[CH:3]=[C:2]([C:32]2([N:35]([CH3:37])[CH3:36])[CH2:33][CH2:34][C:29](=[O:28])[CH2:30][CH2:31]2)[CH:7]=[CH:6][CH:5]=1

Participants

13

Reactant 7

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 6101p-Toluenesulfonic acidHCID 80803,4-dihydro-2H-pyranHCID 115633-BromophenolHCID 25517Ammonium ChlorideHCID 3609778-(Dimethylamino)-1,4-dioxaspiro[4.5]decane-8-carbonitrile

Product 1

HCID 12681766HCID 12681766, compoundYield 48%

Reagents, catalysts & solvents 5

HCID 241BenzeneSolventHCID 887MethanolSolventHCID 3283Diethyl EtherSolvent2×HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A reaction solution consisting of 5.0 gm. (0.029 mole) m-bromophenol, 5.0 gm. dihydropyran, 0.30 gm. p-toluenesulfonic acid, and 80 ml. anhydrous diethyl ether is stirred at 25° C. for four (4) hours. The mixture is washed successively with 25 ml. portions of 1 N aqueous sodium hydroxide, with water, and with brine. The thus washed organic layer is taken to dryness by removing the solvent by evaporation under reduced pressure. There is thus obtained 7.42 gm. of m-(tetrahydropyranyloxy)bromobenzene which is converted to the corresponding Grignard reagent by adding 0.70 gm. magnesium and 60 ml. tetrahydrofuran. To this Grignard is added 1.50 gm. (0.0071 mole) of 4-cyano-4-dimethylaminocyclohexanone ethylene ketal (prepared in Preparation III, Part b, above) dissolved in 30 ml. tetrahydrofuran. This reaction mixture is heated at the reflux temperature for 22 hours. After cooling, the mixture is treated with 10 ml. saturated aqueous ammonium chloride and benzene. The organic solvent portion is initially washed with water and then with brine. The organic solvent is then removed by evaporation under reduced pressure. The residue thus obtained is dissolved in diethyl ether and treated with 4 N ethereal hydrogen chloride until precipitation of the hydrochloride salt is complete. The salt is collected on a filter and then suspended in 25 ml. water containing 1 ml. 2.5 N hydrochloric acid. The acidified mixture is stirred at 25° C. for one hour, when sodium bicarbonate (solid) is added until the pH is 8. This slightly basic mixture is extracted thoroughly with diethyl ether. The ether extracts are combined and the ether removed by evaporation under reduced pressure. The residue thus obtained is transferred to a column of silica gel 1" in cross section by 48" long. The chromatogram is developed with a solvent medium consisting of 0.5 percent ammonia and 7.5 percent methanol in chloroform. Fractions which are shown by thin layer chromatography (TLC) to contain product are collected and combined. The solvent is removed by evaporation under reduced pressure to give 0.96 gm. (48% yield) of crude 4-(m-hydroxyphenyl)-4-dimethylaminocyclohexanone, ethylene ketal having a melting point at 169° to 175° C. An analytical sample is obtained by recrystallization from a mixture of ethyl acetate and cyclohexane. The melting point is 175° to 177° C.

Workup

  1. washThe mixture is washed successively with 25 ml
  2. customby removing the solvent
  3. customby evaporation under reduced pressure
  4. additionby adding 0.70 gm
  5. additionTo this Grignard is added 1.50 gm
  6. temperatureThis reaction mixture is heated at the reflux temperature for 22 hours
  7. temperatureAfter cooling
  8. additionthe mixture is treated with 10 ml
  9. washThe organic solvent portion is initially washed with water
  10. customThe organic solvent is then removed by evaporation under reduced pressure
  11. customThe residue thus obtained
  12. customThe salt is collected on
  13. filtrationa filter
  14. additionwhen sodium bicarbonate (solid) is added until the pH is 8
  15. extractionThis slightly basic mixture is extracted thoroughly with diethyl ether
  16. customthe ether removed by evaporation under reduced pressure
  17. customThe residue thus obtained
  18. customare collected
  19. customThe solvent is removed by evaporation under reduced pressure
  20. customto give 0.96 gm

Sources & evidence

ORD record
ord-83040893a5c840e8a5081d43c02d5f72
Source dataset
uspto-grants-1984_05
Patent number
US04447454

Reaction notes

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