Hydrochloric Acid → HCID 178447921, compound

HRID 2268709Notes

Reaction equation

HRID 2268709 reaction equation
[CH2:1]([CH:4]1[CH2:9][CH2:8][CH:7]([C:10]2[CH:15]=[C:14]([F:16])[C:13](I)=[C:12]([Cl:18])[CH:11]=2)[CH2:6][CH2:5]1)[CH2:2][CH3:3].C(C1CCC(C2C=C(F)C=C(Cl)C=2)CC1)CC.OB(O)[C:38]1[CH:43]=[CH:42][C:41]([F:44])=[C:40]([F:45])[CH:39]=1.FC1C=C(Br)C=CC=1F.COB(OC)OC.Cl.C(=O)([O-])[O-].[K+].[K+]>[Pd].CCCCCCC.C1(C)C=CC=CC=1.C(O)C.O>[CH2:1]([C@H:4]1[CH2:9][CH2:8][C@H:7]([C:10]2[CH:15]=[C:14]([F:16])[C:13]([C:38]3[CH:43]=[CH:42][C:41]([F:44])=[C:40]([F:45])[CH:39]=3)=[C:12]([Cl:18])[CH:11]=2)[CH2:6][CH2:5]1)[CH2:2][CH3:3]

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 8470Trimethyl borateHCID 11430Potassium CarbonateHCID 676754-Bromo-1,2-difluorobenzeneHCID 27343373,4-Difluorobenzeneboronic acidHCID 18332064HCID 18332064, compoundHCID 18332068HCID 18332068, compound

Product 1

HCID 178447921HCID 178447921, compoundYield 91.6%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 8900HeptaneSolventHCID 86587398Ethanol toluene waterSolvent

Procedure

A mixture of 5.0 g (13.1 mmol) of 4-propylcyclohexyl-3-chloro-5-fluoro-4-iodobenzene [prepared by the same method as in the second step of Example 1 with the exception that 4-propylcyclohexyl-3-chloro-5-fluorobenzene was used in place of the 4-propoxycyclohexyl-3-chloro-5-fluorobenzene used in the second step of Example 1], 3.1 g (19.7 mmol) of dihydroxy(3,4-difluorophenyl)borane [prepared by reacting a Grignard reagent, which was prepared in turn from 3,4-difluorobromobenzene, with trimethoxyborane, and then hydrolyzing with hydrochloric acid], 3.6 g (26.3 mmol) of potassium carbonate, 0.5 g of 5% Pd-C, and 50 ml of mixed solvent of toluene/ethanol/water (1/1/1) was heated to reflux for 32 hours. After the catalyst was removed by filtration, the mixture was extracted with 100 ml of toluene. The organic layer thus obtained was washed with water thrice and then dried over anhydrous magnesium sulfate. The solvent was distilled off under a reduce pressure and the residue thus obtained was subjected to silica gel column chromatography (eluent: heptane) to obtain 4.4 g of a crude 4′-(trans-4-propyl-cyclohexyl)-2′-chloro-3,4,6′-trifluorobiphenyl. This product was recrystallized from a mixed solvent of ethanol/ethyl acetate to obtain 0.9 g of the subject compound. (Yield: 18.3%)

Workup

  1. customprepared
  2. temperaturewas heated
  3. temperatureto reflux for 32 hours
  4. customAfter the catalyst was removed by filtration
  5. extractionthe mixture was extracted with 100 ml of toluene
  6. customThe organic layer thus obtained
  7. washwas washed with water thrice
  8. dry with materialdried over anhydrous magnesium sulfate
  9. distillationThe solvent was distilled off under a reduce pressure
  10. customthe residue thus obtained

Sources & evidence

ORD record
ord-a364243d747141de9bb17ffe8b3f9ac7
Source dataset
uspto-grants-2001_12
Patent number
US06329027B1

Reaction notes

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