Sodium Carbonate → 1-Pyridin-3-yl-4-(2'-trifluoromethoxybiphenyl-4-yloxy)pentan-3-ol

HRID 380010Notes

Reaction equation

HRID 380010 reaction equation
[OH:1][C@H:2]([CH2:15][CH2:16][C:17]1[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=1)[C@H:3]([CH3:14])[O:4][C:5]1[CH:10]=[CH:9][C:8](B(O)O)=[CH:7][CH:6]=1.Br[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[O:30][C:31]([F:34])([F:33])[F:32].C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.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>[N:19]1[CH:20]=[CH:21][CH:22]=[C:17]([CH2:16][CH2:15][CH:2]([OH:1])[CH:3]([O:4][C:5]2[CH:10]=[CH:9][C:8]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[O:30][C:31]([F:32])([F:34])[F:33])=[CH:7][CH:6]=2)[CH3:14])[CH:18]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27772661-Bromo-2-(trifluoromethoxy)benzeneHCID 54413593(1S,2R)-4-(2-hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acid

Product 1

HCID 183676241-Pyridin-3-yl-4-(2'-trifluoromethoxybiphenyl-4-yloxy)pentan-3-olYield 69.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

Prepared according to the method described in Example 12b) from (1S,2R)-4-(2-hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acid (0.150 g, Example 33), 2-bromo(trifluoromethyloxy)benzene (0.26 g), 2M aqueous sodium carbonate (0.50 ml) and tetrakis(triphenylphosphine)palladium (0) (0.025 g) in ethanol (3 ml). The reaction mixture was heated in a sealed vial at 80° C. for 2 hours. After cooling, the solution was is concentrated under reduced pressure and taken up in acetone and filtered through a small plug of silica. The filtrate was concentrated under reduced pressure, dissolved in dichloromethane, filtered and purified by normal-phase HPLC eluting with a gradient of 0-25% ethanol in dichloromethane to give an oil (0.145 g).

Workup

  1. customPrepared
  2. temperatureAfter cooling
  3. concentrationthe solution was is concentrated under reduced pressure
  4. filtrationfiltered through a small plug of silica
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. dissolutiondissolved in dichloromethane
  7. filtrationfiltered
  8. custompurified by normal-phase HPLC
  9. washeluting with a gradient of 0-25% ethanol in dichloromethane

Sources & evidence

ORD record
ord-73714403138e47eab3dca11a4fe81f81
Source dataset
uspto-grants-2001_10
Patent number
US06300352B1

Reaction notes

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