Sodium Carbonate → HCID 20692746, compound

HRID 380035Notes

Reaction equation

HRID 380035 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.N1([NH:28][S:29]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34](Br)[CH:33]=2)(=[O:31])=[O:30])CCCC1.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][C@@H:2]([OH:1])[C@@H:3]([O:4][C:5]2[CH:10]=[CH:9][C:8]([C:36]3[CH:35]=[CH:34][CH:33]=[C:32]([S:29]([N:28]4[CH2:14][CH2:3][CH2:2][CH2:15]4)(=[O:30])=[O:31])[CH:37]=3)=[CH:7][CH:6]=2)[CH3:14])[CH:18]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 54413593(1S,2R)-4-(2-hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acidHCID 71436066HCID 71436066, compound

Product 1

HCID 20692746HCID 20692746, compoundYield 117.9%

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), 3-bromobenzenesulfonic acid, pyrrolidinyl amide (0.290 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 gum, which was further purified by reverse-phase HPLC to give the title compound as a foam (0.137 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 gum, which
  13. customwas further purified by reverse-phase HPLC

Sources & evidence

ORD record
ord-a496955efd834e3fb4de5c61311ce277
Source dataset
uspto-grants-2001_10
Patent number
US06300352B1

Reaction notes

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