Sodium Carbonate → HCID 57047089, compound

HRID 380039Notes

Reaction equation

HRID 380039 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.[CH3:23][NH:24][C:25](=[O:34])[C:26]1[CH:31]=[CH:30][C:29]([CH3:32])=[C:28](Br)[CH:27]=1.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>[CH3:23][NH:24][C:25]([C:26]1[CH:27]=[C:28]([C:8]2[CH:9]=[CH:10][C:5]([O:4][C@@H:3]([CH3:14])[C@H:2]([OH:1])[CH2:15][CH2:16][C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)=[CH:6][CH:7]=2)[C:29]([CH3:32])=[CH:30][CH:31]=1)=[O:34]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 54413593(1S,2R)-4-(2-hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acidHCID 79466300HCID 79466300, compound

Product 1

HCID 57047089HCID 57047089, compound

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 (0.20 g, Example 33 (0.290 g), 3-bromo-4-methylbenzoic acid, methyl amide (0.30 g), 2M aqueous sodium carbonate (0.66 ml) and tetrakis(triphenylphosphine)palladium(0) (0.038 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 an oil, which was further purified by column chromatography over silica gel eluting with ethyl acetate:ethanol (9:1) to give the title compound as a foam(0.20 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 an oil, which
  13. customwas further purified by column chromatography over silica gel eluting with ethyl acetate:ethanol (9:1)

Sources & evidence

ORD record
ord-1e08a867a6cd4981a3f2ae8b8b8e0834
Source dataset
uspto-grants-2001_10
Patent number
US06300352B1

Reaction notes

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