Sodium Carbonate → HCID 20692737, compound

HRID 379980

Reaction equation

HRID 379980 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:35]2[CH:36]=[CH:31][CH:32]=[C:33]([CH2:37][C:38]([NH:40][CH3:41])=[O:39])[CH:34]=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 20692737HCID 20692737, compoundYield 77%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

A solution of (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 (0.21 g, Example 12a)), 2M aqueous sodium carbonate (0.57 ml) and tetrakis(triphenylphosphine)palladium (0) (0.1 g) in toluene (5 ml) and ethanol (2 ml) was heated at 100° C. for 4 hours. After cooling, the solution was concentrated under reduced pressure. Concentrated hydrochloric acid (1 ml) was added to a solution of the residue in methanol (5 ml). The suspension was stirred at room temperature for 18 hours. The mixture was concentrated under reduced pressure and the residue partitioned between ether and water. The aqueous layer was neutralised and extracted with dichloromethane (2×50 ml). 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 0-25% ethanol in dichloromethane to give the title compound as an oil (0.15 g).

Workup

  1. temperatureAfter cooling
  2. concentrationthe solution was concentrated under reduced pressure
  3. additionConcentrated hydrochloric acid (1 ml) was added to a solution of the residue in methanol (5 ml)
  4. concentrationThe mixture was concentrated under reduced pressure
  5. customthe residue partitioned between ether and water
  6. extractionextracted with dichloromethane (2×50 ml)
  7. dry with materialThe combined extracts were dried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by normal-phase HPLC
  11. washeluting with a gradient of 0-25% ethanol in dichloromethane

Sources & evidence

ORD record
ord-3598a98110e447a9b81a5785a84888de
Source dataset
uspto-grants-2001_10
Patent number
US06300352B1

Linked notes

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