Sodium Carbonate → HCID 20692739, compound

HRID 379988

Reaction equation

HRID 379988 reaction equation
[Si]([O:8][C@H:9]([CH2:22][CH2:23][C:24]1[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=1)[C@H:10]([CH3:21])[O:11][C:12]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14][CH:13]=1)(C(C)(C)C)(C)C.Br[C:31]1[CH:32]=[C:33]([CH2:37][C:38]([NH:40][CH3:41])=[O:39])[CH:34]=[CH:35][CH:36]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.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:8][C@H:9]([CH2:22][CH2:23][C:24]1[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=1)[C@H:10]([CH3:21])[O:11][C:12]1[CH:13]=[CH:14][C:15]([C:36]2[CH:35]=[CH:34][C:33]([CH2:37][C:38]([NH:40][CH3:41])=[O:39])=[CH:32][CH:31]=2)=[CH:16][CH:17]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 186685292-(3-bromophenyl)-N-methylacetamideHCID 54020751(1S,2R)-4-[2-(tert-butyldimethylsilanyloxy)-1-methyl-4-pyridin-3-ylbutoxy]benzeneboronic acid

Product 1

HCID 20692739HCID 20692739, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

Prepared according to the method described in Example 12b) from (1S,2R)-4-[2-(tert-butyldimethylsilanyloxy)-1-methyl-4-pyridin-3-ylbutoxy]benzeneboronic acid (0.20 g, Example 11)), 2-(3-bromophenyl)-N-methyl-acetamide (0.244 g, Example 24a)), 2M aqueous sodium carbonate (0.265 ml) and tetrakis(triphenylphosphine)palladium (0) (0.1 g) in toluene (5 ml) and ethanol (2 ml). The reaction was heated at 110° C. for 6 hours. After cooling, the solution was concentrated under reduced pressure the residue was dissolved in methanol (10 ml), concentrated hydrochloric acid (1 ml) was added and the solution stirred at room temperature for 18 hours. The mixture was concentrated under reduced pressure the residue was neutralised using saturated sodium hydrogen carbonate and extracted with ethyl acetate. The combined extracts were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal-phase HPLC eluting with a gradient of 0-10% ethanol in dichloromethane to give the title compound as an oil which was converted to the oxalic acid salt by treatment with a saturated ethereal solution of oxalic acid to give the title compound as a gum (0.123 g).

Workup

  1. customPrepared
  2. temperatureAfter cooling
  3. concentrationthe solution was concentrated under reduced pressure the residue
  4. dissolutionwas dissolved in methanol (10 ml)
  5. additionconcentrated hydrochloric acid (1 ml) was added
  6. concentrationThe mixture was concentrated under reduced pressure the residue
  7. extractionextracted with ethyl acetate
  8. dry with materialThe combined extracts were dried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by normal-phase HPLC
  12. washeluting with a gradient of 0-10% ethanol in dichloromethane

Sources & evidence

ORD record
ord-e8910b04050d4fc19ba947fab5b9922f
Source dataset
uspto-grants-2001_10
Patent number
US06300352B1

Linked notes

Loading…