Triethylamine → HCID 58444571, compound

HRID 1509767Notes

Reaction equation

HRID 1509767 reaction equation
[CH2:1]([CH:3]1[CH2:8][O:7][CH:6]([C:9]2[CH:14]=[CH:13][C:12](B3OC(C)(C)C(C)(C)O3)=[C:11]([F:24])[CH:10]=2)[CH2:5][CH2:4]1)[CH3:2].Br[C:26]1[CH:31]=[C:30]([F:32])[C:29]([C:33]([F:48])([F:47])[O:34][C:35]2[CH:36]=[C:37]([F:46])[C:38]([C:42]([F:45])([F:44])[F:43])=[C:39]([F:41])[CH:40]=2)=[C:28]([F:49])[CH:27]=1.C(N(CC)CC)C.C(=O)([O-])O.[K+]>C1COCC1.O.CC1C=CC=CC=1[P](C1C=CC=CC=1C)([Pd](Cl)(Cl)[P](C1=C(C)C=CC=C1)(C1C=CC=CC=1C)C1C=CC=CC=1C)C1C=CC=CC=1C.CC(OC)(C)C>[F:41][C:39]1[CH:40]=[C:35]([CH:36]=[C:37]([F:46])[C:38]=1[C:42]([F:43])([F:45])[F:44])[O:34][C:33]([F:47])([F:48])[C:29]1[C:28]([F:49])=[CH:27][C:26]([C:12]2[CH:13]=[CH:14][C:9]([CH:6]3[CH2:5][CH2:4][CH:3]([CH2:1][CH3:2])[CH2:8][O:7]3)=[CH:10][C:11]=2[F:24])=[CH:31][C:30]=1[F:32]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 516893Potassium BicarbonateHCID 58444567HCID 58444567, compoundHCID 58444590HCID 58444590, compound

Product 1

HCID 58444571HCID 58444571, compound

Reagents, catalysts & solvents 4

HCID 178424406HCID 178424406, compoundCatalystHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
50 °C

Procedure

5.20 g (15.0 mmol) of 5-ethyl-2-[3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]tetrahydropyran are initially introduced in 35 ml of THF together with 6.93 g (15.0 mmol) of 5-((4-bromo-2,6-difluorophenyl)-difluoromethoxy)-1,3-difluoro-2-(trifluoromethyl)benzene. 590 mg (0.75 mmol) of bis(tri-o-tolylphosphine)palladium(II) chloride and 0.1 ml (0.75 mmol) of triethylamine are added. The mixture is heated to 50° C., and a solution of 2.41 g (24.0 mmol) of potassium hydrogencarbonate in 15 ml of water is added. After 3 h at this temperature, water and MTBE are added, and the organic phase is separated off. The aqueous phase is washed with MTBE, and the combined organic phases are washed with saturated sodium chloride solution and dried using sodium sulfate. The solution is concentrated to dryness, and the crude product is purified by column chromatography (SiO2, n-heptane:toluene=1:1). The further purification is carried out by recrystallisation from ethanol and n-heptane, giving 2-{4′-[(3,5-difluoro-4-trifluoromethylphenoxy)difluoromethyl]-2,3′,5′-trifluorobiphenyl-4-yl}-5-ethyltetrahydropyran as a colourless solid having an m.p. of 90° C.

Workup

  1. customthe organic phase is separated off
  2. washThe aqueous phase is washed with MTBE
  3. washthe combined organic phases are washed with saturated sodium chloride solution
  4. customdried
  5. concentrationThe solution is concentrated to dryness
  6. customthe crude product is purified by column chromatography (SiO2, n-heptane:toluene=1:1)
  7. customThe further purification
  8. customis carried out by recrystallisation from ethanol and n-heptane

Sources & evidence

ORD record
ord-6b6fca11ffde44caa23c7ed1b1b426d8
Source dataset
uspto-grants-2012_07
Patent number
US08211513B2

Reaction notes

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