Dimethylformamide → Methyl 2'-fluoro-5'-(methyloxy)-2-((1R,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-yl)-1,1'-biphenyl-4-carboxylate

HRID 2098923Notes

Reaction equation

HRID 2098923 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][C:13]([C:16]([O:18][CH3:19])=[O:17])=[CH:12][C:11]=1I.CN(C=O)C.[CH3:26][C@:27]12[C:33]([CH3:35])([CH3:34])[C@H:30]([CH2:31][CH2:32]1)[CH:29]=[C:28]2B(O)O.C(=O)([O-])[O-].[K+].[K+]>[Cl-].[Na+].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>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][C:13]([C:16]([O:18][CH3:19])=[O:17])=[CH:12][C:11]=1[C:28]1[C@@:27]2([CH3:26])[C:33]([CH3:35])([CH3:34])[C@@H:30]([CH:29]=1)[CH2:31][CH2:32]2

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 51051605((1s,4r)-1,7,7-Trimethylbicyclo[2.2.1]hept-2-en-2-yl)boronic acidHCID 57705628Methyl 2'-fluoro-2-iodo-5'-(methyloxy)-1,1'-biphenyl-4-carboxylate

Product 1

HCID 57706090Methyl 2'-fluoro-5'-(methyloxy)-2-((1R,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-yl)-1,1'-biphenyl-4-carboxylateYield 81%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of T10.4 (0.200 g, 0.52 mmol) in DMF (4.00 mL, 52 mmol) at 23° C. was added (1S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-ylboronic acid (0.19 g, 1.0 mmol, commercially available from Combi-Blocks, Cat. No. BB-2567), potassium carbonate (0.21 g, 1.6 mmol), and then tetrakis(triphenylphosphine)palladium (0.060 g, 0.052 mmol). The mixture was heated at 90° C. for 19 hours and then cooled to room temperature. The reaction was diluted with brine and extracted three times with EtOAc. After drying over anhydrous magnesium sulfate and filtering, the organic solvent was removed under reduced pressure and the product was purified on silica gel (0-10% EtOAc in hexanes) to yield T10.5 as a colorless oil (0.165 g, 81% yield).

Workup

  1. temperaturecooled to room temperature
  2. extractionextracted three times with EtOAc
  3. dry with materialAfter drying over anhydrous magnesium sulfate
  4. filtrationfiltering
  5. customthe organic solvent was removed under reduced pressure
  6. customthe product was purified on silica gel (0-10% EtOAc in hexanes)

Sources & evidence

ORD record
ord-b72cbba6f6534b6495b84deea4e59596
Source dataset
uspto-grants-2013_05
Patent number
US08450522B2

Reaction notes

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