Hydrochloric Acid → HCID 45120067, compound

HRID 2220322Notes

Reaction equation

HRID 2220322 reaction equation
Br[C:2]1([F:12])[CH2:10][CH2:9][C:5]2[S:6][CH:7]=[CH:8][C:4]=2[C:3]1=[O:11].C(=O)([O-])[O-].[Li+].[Li+].[Br-].[Li+].Cl>CN(C)C=O>[F:12][C:2]1[CH:10]=[CH:9][C:5]2[S:6][CH:7]=[CH:8][C:4]=2[C:3]=1[OH:11]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11125Lithium CarbonateHCID 82050Lithium BromideHCID 59769746HCID 59769746, compound

Product 1

HCID 45120067HCID 45120067, compoundYield 79.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Heat a mixture of 5-bromo-5-fluoro-6,7-dihydro-5H-benzo[b]thiophen-4-one (6.97 g, 28.0 mmol, 1 equiv.), lithium carbonate (4.34 g, 58.7 mmol, 2.1 equiv.), and lithium bromide (5.61 g, 64.6 mmol, 2.3 equiv.) in dry dimethylformamide (150 mL) at 150° C. (internal temperature) for 2 hours. Cool the reaction mixture to room temperature, add ice water, and then carefully add 5N HCl until gas evolution ceases and the mixture is acidic. Add ethyl acetate, separate the layers, and extract the aqueous layer with ethyl acetate (3 times). Extract the combined organic extracts with 2N sodium hydroxide (2 times), reacidify the aqueous layers with hydrochloric acid, and then re-extract the aqueous layer with dichloromethane (3 times). Dry the dichloromethane extracts over anhydrous magnesium sulfate, filter, and concentrate under reduced pressure. Purify the resultant crude material by medium pressure liquid chromatography eluting with 0 to 10% ethyl acetate in hexanes to afford the title compound as a colorless solid (3.738 g, 79%). δH (400 MHz, CDCl3) 5.35 (br s, 1H), 7.13 (dd, 1H, J=10, 8 Hz), 7.34 (ddd, 1H, J=8, 4, 1 Hz), 7.42 (d, 1H, J=6 Hz), 7.49 (dd, 1H, J=6, 1 Hz).

Workup

  1. temperatureHeat
  2. customAdd ethyl acetate, separate the layers
  3. extractionextract the aqueous layer with ethyl acetate (3 times)
  4. extractionExtract the combined organic extracts with 2N sodium hydroxide (2 times)
  5. extractionre-extract the aqueous layer with dichloromethane (3 times)
  6. dry with materialDry the dichloromethane
  7. filtrationfilter
  8. concentrationconcentrate under reduced pressure
  9. customPurify the resultant crude material by medium pressure liquid chromatography
  10. washeluting with 0 to 10% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-d05b1caf1792435fa598aa206bdec44f
Source dataset
uspto-grants-2008_08
Patent number
US07417064B2

Reaction notes

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