Hydrochloric Acid → HCID 68536142, compound

HRID 1985105Notes

Reaction equation

HRID 1985105 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[C:4]([CH2:14][NH:15][CH2:16][C@@H:17]([OH:32])[C@@H:18]([NH:28][C:29](=[O:31])[CH3:30])[CH2:19][C:20]2[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([F:27])[CH:21]=2)[CH:3]=1.C([Sn](CCCC)(CCCC)[C:38]([O:40]CC)=[CH2:39])CCC.[ClH:51]>C1(C)C=CC=CC=1.CCOCC>[ClH:51].[C:38]([C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[C:4]([CH2:14][NH:15][CH2:16][C@@H:17]([OH:32])[C@@H:18]([NH:28][C:29](=[O:31])[CH3:30])[CH2:19][C:20]2[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([F:27])[CH:21]=2)[CH:3]=1)(=[O:40])[CH3:39]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 58909328HCID 58909328, compound

Product 1

HCID 68536142HCID 68536142, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
100 °C

Procedure

To N-[(1S,2R)-3-{[(4-bromo-1,1′-biphenyl-2-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]acetamide (120 mg, 0.24 mmol) in toluene (1 mL) was added tributyl(1-ethoxyvinyl)tin (100 μL, 0.28 mmol) and bis-triphenylphoshine palladium(II) dichloride (10 mg, 0.012 mmol), and the reaction was heated at 100° C. 3 h under N2. The solution was cooled to room temperature, 1N hydrochloric acid (1 mL) was added, and the mixture was stirred 20 min. The mixture was partitioned, and the organics were washed with saturated potassium fluoride (aq). The reaction mixture was dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica gel, 8% methanol/methylene chloride) provided an oil. The residue was dissolved in ether, precipitated with excess 1N HCl in ether, and concentrated to provide the title compound (11 mg). ESI MS m/z 467.28 [M+H]+.

Workup

  1. custom3 h
  2. temperatureThe solution was cooled to room temperature
  3. customThe mixture was partitioned
  4. washthe organics were washed with saturated potassium fluoride (aq)
  5. dry with materialThe reaction mixture was dried (sodium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash column chromatography (silica gel, 8% methanol/methylene chloride)
  9. customprovided an oil
  10. customprecipitated with excess 1N HCl in ether
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-1c05855ff7ba486e933e887411fe645c
Source dataset
uspto-grants-2009_06
Patent number
US07544717B2

Reaction notes

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