Propargyl bromide → HCID 58934812, compound

HRID 854973Notes

Reaction equation

HRID 854973 reaction equation
[CH2:1](Br)[C:2]#[CH:3].[OH-].[Na+].I[C:8]1[CH:17]=[C:16]2[C:11]([CH:12]=[C:13]([C:22]([OH:24])=[O:23])[CH:14]([C:18]([F:21])([F:20])[F:19])[O:15]2)=[CH:10][CH:9]=1>C1COCC1.O.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>[CH:2]1([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13]([C:22]([OH:24])=[O:23])[CH:14]([C:18]([F:21])([F:20])[F:19])[O:15]3)=[CH:10][CH:9]=2)[CH2:3][CH2:1]1

Participants

7

Reactant 3

HCID 7842Propargyl bromideHCID 14798Sodium HydroxideHCID 695190647-iodo-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid

Product 1

HCID 58934812HCID 58934812, compoundYield 40%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 178418397HCID 178418397, compoundSolvent

Procedure

To a suspension of (9-BBN)2 (1.96 g, 8.7 mmol) in 10 mL THF was added propargyl bromide (0.53 g, 4.4 mmol). After heating for 2 h and cooling to room temperature, NaOH (0.52 g, 13 mmol) in 4.3 mL of H2O was added and the reaction was stirred for 1 h. In a separate flask under argon was added the title product of Example 146 Step 1 in 5 mL of THF and Pd(PPh3)4. The reaction from the original flask was transferred to the second flask via cannula. After refluxing for 18 h and cooling to room temperature, 25 mL of H2O was added. The organic solvent was removed from the reaction under vacuum. The aqueous layer was extracted three times with 70 mL EtOAc. The combined organic extractions were washed one time with 50 mL of 1 N HCl and one time with 50 mL of saturated brine. Following drying over MgSO4 and concentrating under vacuum, the product was purified by flash column chromatography and reverse phase chromatography on YMC ODS-AQ in MeOH/H2O to yield desired product (0.40 g, 40%).

Workup

  1. temperatureAfter heating for 2 h
  2. customThe reaction from the original flask
  3. temperatureAfter refluxing for 18 h
  4. temperaturecooling to room temperature
  5. customThe organic solvent was removed from the reaction under vacuum
  6. extractionThe aqueous layer was extracted three times with 70 mL EtOAc
  7. extractionThe combined organic extractions
  8. washwere washed one time with 50 mL of 1 N HCl and one time with 50 mL of saturated brine
  9. dry with materialFollowing drying over MgSO4
  10. concentrationconcentrating under vacuum
  11. customthe product was purified by flash column chromatography

Sources & evidence

ORD record
ord-e27ffc9b4e7043099cd1134ce02a3beb
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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