Allyl bromide → HCID 86622327, compound

HRID 501695Notes

Reaction equation

HRID 501695 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C@H:6]([OH:18])[CH2:7][C@@H:8]2[NH:11][C:12](=[O:17])[C:13]([F:16])([F:15])[F:14])=[CH:4][CH:3]=1.[H-].[Na+].[CH2:21](Br)[CH:22]=[CH2:23]>CN(C=O)C>[CH2:23]([O:18][C@H:6]1[C:5]2[C:9](=[CH:10][C:2]([Br:1])=[CH:3][CH:4]=2)[C@@H:8]([NH:11][C:12](=[O:17])[C:13]([F:16])([F:14])[F:15])[CH2:7]1)[CH:22]=[CH2:21]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 24758Sodium hydrideHCID 86622328HCID 86622328, compound

Product 1

HCID 86622327HCID 86622327, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Step Z (5). A solution of 1.7 g (5.25 mmol) of N-((1S,3R)-6-bromo-3-hydroxy-2,3-dihydro-1H-inden-1-yl)-2,2,2-trifluoroacetamide from step Z (4) was dissolved in 30 mL of DMF, and a suspension of 60% NaH in mineral oil (630 mg, 15.75 mmol) was added in portions to minimize gas evolution. The resulting reaction mixture was stirred at rt for 10 min, and then allyl bromide (953 mg, 7.8 mmol) was added. After stirring at rt for 3 h, the starting material was consumed. The reaction solution was diluted with 60 mL of ether and the remaining NaH was slowly quenched with water. Brine (20 mL) was then added, and the organic layer was removed followed by extraction of the aqueous layer with 2 more portions of ether. The combined organics were dried and concentrated, and the crude product was purified by chromatography eluting with a gradient of 0 to 15% EtOAc in hexanes to provide 1.26 g (74% yield) of N-((1S,3R)-3-(allyloxy)-6-bromo-2,3-dihydro-1H-inden-1-yl)-2,2,2-trifluoroacetamide. 1H NMR (500 MHz, CDCl3) δ ppm 2.06 (ddd, J=13.89, 3.05, 2.90 Hz, 1H) 2.70 (ddd, J=13.89, 7.17, 5.49 Hz, 1H) 4.07 (ddd, J=5.65, 1.53, 1.37 Hz, 2H) 4.80 (dd, J=5.65, 2.59 Hz, 1H) 5.22 (dd, J=10.38, 1.22 Hz, 1H) 5.29 (ddd, J=17.32, 3.13, 1.53 Hz, 1H) 5.37-5.44 (m, 1H) 5.84-5.95 (m, 1H) 6.81 (d, J=7.63 Hz, 1H) 7.30 (d, J=7.93 Hz, 1H) 7.49 (dd, J=7.93, 1.83 Hz, 1H) 7.58 (d, J=1.53 Hz, 1H).

Workup

  1. additionwas added in portions
  2. customThe resulting reaction mixture
  3. stirringAfter stirring at rt for 3 h
  4. customthe starting material was consumed
  5. additionThe reaction solution was diluted with 60 mL of ether
  6. customthe remaining NaH was slowly quenched with water
  7. additionBrine (20 mL) was then added
  8. customthe organic layer was removed
  9. extractionfollowed by extraction of the aqueous layer with 2 more portions of ether
  10. customThe combined organics were dried
  11. concentrationconcentrated
  12. customthe crude product was purified by chromatography
  13. washeluting with a gradient of 0 to 15% EtOAc in hexanes

Sources & evidence

ORD record
ord-e82ec6676da0474d86212759fe5b3220
Source dataset
uspto-grants-2010_08
Patent number
US07772221B2

Reaction notes

Loading…