Potassium Phosphate, Tribasic → (3,5-Dimethyl-3'-trifluoromethoxy-biphenyl-4-yl)-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone

HRID 1692394Notes

Reaction equation

HRID 1692394 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([C:9]([N:11]2[CH2:16][CH2:15][CH:14]([N:17]3[CH2:21][CH2:20][CH2:19][CH2:18]3)[CH2:13][CH2:12]2)=[O:10])=[C:4]([CH3:22])[CH:3]=1.[F:23][C:24]([F:36])([F:35])[O:25][C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:22][C:4]1[CH:3]=[C:2]([C:28]2[CH:29]=[CH:30][CH:31]=[C:26]([O:25][C:24]([F:23])([F:35])[F:36])[CH:27]=2)[CH:7]=[C:6]([CH3:8])[C:5]=1[C:9]([N:11]1[CH2:16][CH2:15][CH:14]([N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[CH2:13][CH2:12]1)=[O:10]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27343853-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 66901599(4-Bromo-2,6-dimethyl-phenyl)-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone2×

Product 1

HCID 25190014(3,5-Dimethyl-3'-trifluoromethoxy-biphenyl-4-yl)-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanoneYield 77%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a degassed solution of 0.130 g (0.35 mmol) of (4-bromo-2,6-dimethyl-phenyl)-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone (intermediate 1) and 0.147 g (0.70 mmol) of 3-trifluoromethoxy-phenyl boronic acid in 5 ml of DMF was added 2.50 ml of tribasic potassium phosphate solution (2M in water) drop by drop, followed by 0.022 g (0.019 mmol) of tetrakis-(triphenylphosphine)-palladium. This reaction mixture was stirred at 80° C. for two hours and subsequently cooled down to RT, then poured into crashed ice and extracted three times with CH2Cl2; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 95:5) to give 0.12 g (77%) of the title compound as light yellow amorphous solid. MS: 447.2 (MH+).

Workup

  1. temperaturesubsequently cooled down to RT
  2. additionpoured
  3. extractionextracted three times with CH2Cl2
  4. washthe organic phases were washed with water
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 95:5)

Sources & evidence

ORD record
ord-a470e3353d50409e8ad58284493018a9
Source dataset
uspto-grants-2012_04
Patent number
US08153805B2

Reaction notes

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