Sodium Carbonate → (2S,3R)-3-{4-[3-hydroxy-5-(3-pyridyl)pentan-2-yloxy]phenyl}phenyloxyacetic acid, amide

HRID 380009Notes

Reaction equation

HRID 380009 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:25]=[C:26]([CH:32]=[CH:33][CH:34]=1)[O:27][CH2:28][C:29]([NH2:31])=[O:30].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>[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]([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:24]2[CH:25]=[C:26]([O:27][CH2:28][C:29]([NH2:31])=[O:30])[CH:32]=[CH:33][CH:34]=2)=[CH:7][CH:6]=1)[CH3:14]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 78183782-(3-Bromophenoxy)acetamideHCID 54413593(1S,2R)-4-(2-hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acid

Product 1

HCID 59970482(2S,3R)-3-{4-[3-hydroxy-5-(3-pyridyl)pentan-2-yloxy]phenyl}phenyloxyacetic acid, amideYield 68.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
90 °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-(3-bromophenoxy)acetamide (0.230 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 at 90° C. for 4 hours. After cooling, the solution was concentrated under reduced pressure, taken up in ethanol and concentrated again (twice). The residue was triturated with acetone and then filtered through silica gel. 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 a colourless solid, which was recrystallised from boiling ethyl acetate:isohexane (1:1) to give the title compound as a solid (0.138 g).

Workup

  1. customPrepared
  2. temperatureAfter cooling
  3. concentrationthe solution was concentrated under reduced pressure
  4. concentrationconcentrated again (twice)
  5. customThe residue was triturated with acetone
  6. filtrationfiltered through silica gel
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. dissolutiondissolved in dichloromethane
  9. filtrationfiltered
  10. custompurified by normal-phase HPLC
  11. washeluting with a gradient of 0-25% ethanol in dichloromethane
  12. customto give a colourless solid, which
  13. customwas recrystallised

Sources & evidence

ORD record
ord-1f0df8ee2fae43978cb528160a2e1e87
Source dataset
uspto-grants-2001_10
Patent number
US06300352B1

Reaction notes

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