Dimethylformamide → 2,3-Dihydrobenzofuran-6-carbaldehyde

HRID 2264152Notes

Reaction equation

HRID 2264152 reaction equation
Br[C:2]1[CH:10]=[CH:9][C:5]2[CH2:6][CH2:7][O:8][C:4]=2[CH:3]=1.C([Li])CCC.CN([CH:19]=[O:20])C>C1COCC1.CCCCCC>[O:8]1[C:4]2[CH:3]=[C:2]([CH:19]=[O:20])[CH:10]=[CH:9][C:5]=2[CH2:6][CH2:7]1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 112526166-Bromo-2,3-dihydro-1-benzofuranHCID 178418339Butyllithium

Product 1

HCID 149643942,3-Dihydrobenzofuran-6-carbaldehyde

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

To an cooled solution (−78° C. internal temp) of 1 g of 6-bromo-2,3-dihydro-1-benzofuran (prepared as described by Z. J. Song, M. Zhao, L. Frey, J. Li, L. Tan, C. Y. Chen, D. M. Tschaen, R. Tillyer, E. J. J. Grabowski, R. Volante, P. J. Reider, Y. Kato, S. Okada, T. Nemoto, H. Sato, A. Akao, T. Mase, Organic Letters, 2001, Vol. 3, No. 21, 3357-3360) in 20 mL of anhydrous THF was added 4 mL of 2.5 M n-butyllithium in hexane. After stirring 10 min at −78° C., 0.5 mL of anhydrous DMF was added and the mixture allowed to warm to −20° C., quenched with 20 mL of 3N HCl and extracted into 2×50 mL of ether. Combined extracts dried over MgSO4 and concentrated under reduced pressure. Purification by flash chromatography (0-20% ethyl acetate in hexanes) gave the product as white crystalline solid. MS (m+1)=149.1; 1H NMR (400 MHz, CDCl3) 9.9 (s, 1H), 7.4 (m, 2H), 7.3 (s, 1H), 4.62 (t, 2H), 3.28 (t, 4H).

Workup

  1. temperatureto warm to −20° C.
  2. customquenched with 20 mL of 3N HCl
  3. extractionextracted into 2×50 mL of ether
  4. dry with materialCombined extracts dried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customPurification by flash chromatography (0-20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-843e3c2b701949c494ffab7051276bc8
Source dataset
uspto-grants-2010_12
Patent number
US07855201B2

Reaction notes

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