Hydrochloric Acid → HCID 178448025, compound

HRID 2214322Notes

Reaction equation

HRID 2214322 reaction equation
[CH2:1]([C@H:4]1[CH2:9][CH2:8][C@H:7]([C@H:10]2[CH2:15][CH2:14][C@H:13]([C:16]3[CH:21]=[C:20]([F:22])[CH:19]=[C:18]([F:23])[CH:17]=3)[CH2:12][CH2:11]2)[CH2:6][CH2:5]1)[CH2:2][CH3:3].C([Li])CCC.CCCCCC.[C:35]1([C@@H:41]([CH3:45])[C:42](Cl)=[O:43])[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.Cl>[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCCC1>[F:23][C:18]1[CH:17]=[C:16]([C@H:13]2[CH2:14][CH2:15][C@H:10]([C@H:7]3[CH2:6][CH2:5][C@H:4]([CH2:1][CH2:2][CH3:3])[CH2:9][CH2:8]3)[CH2:11][CH2:12]2)[CH:21]=[C:20]([F:22])[C:19]=1[C:42](=[O:43])[C@@H:41]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[CH3:45]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 7161075(R)-2-phenylpropionyl chlorideHCID 178418244HCID 178418244, compoundHCID 178448024HCID 178448024, compound

Product 1

HCID 178448025HCID 178448025, compoundYield 29.2%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

To a tetrahydrofuran 50 ml solution of 10 g (0.031 mol) of 1-[trans-4-(trans-4-propylcyclohexyl)cyclohexyl]-3,5-difluorobenzene, a n-butyllithium/hexane solution (1.6M, 0.041 mol) was dropwise added over a period of 1 hour at −60° C., followed by stirring for 2 hours at the same temperature. Then, a tetrahydrofuran 30 ml solution of 5.5 g (0.041 mol) of zinc chloride was dropwise added thereto over a period of 2 hours at −60° C., followed by stirring for 1 hour at room temperature. After 0.72 g (0.62 mmol) of tetrakis(triphenylphosphine)palladium was added thereto, a tetrahydrofuran 10 ml solution of 4.7 g (0.041 mol) of (R)-2-phenylpropionyl chloride was dropwise added thereto over a period of 1 hour at room temperature, followed by stirring at room temperature overnight. 43 ml of 1M hydrochloric acid was dropwise added to the reaction solution at room temperature, followed by stirring at the same temperature for 1 hour. After extraction with toluene from the solution, washing with water, drying, distillation of the solvent and recrystallization were carried out to obtain 4.1 g of (R)-1-[2,6-difluoro-4-[trans-4-(trans-4-propylcyclohexyl)cyclohexyl]phenyl]-2-phenyl-1-propanone.

Workup

  1. waitover a period of 2 hours at −60° C.
  2. stirringby stirring for 1 hour at room temperature
  3. waitover a period of 1 hour at room temperature
  4. stirringby stirring at room temperature overnight
  5. stirringby stirring at the same temperature for 1 hour
  6. extractionAfter extraction with toluene from the solution
  7. washwashing with water
  8. customdrying
  9. distillationdistillation of the solvent and recrystallization

Sources & evidence

ORD record
ord-25824e6950eb4cdfa4d0962098181c41
Source dataset
uspto-grants-2006_09
Patent number
US07108895B2

Reaction notes

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