Boron trifluoride → 2-[2-(3-Hydroxy-propenyl)-benzofuran-3-ylmethyl]-pyrrolidine-1-carboxylic acid benzyl ester

HRID 1054013Notes

Reaction equation

HRID 1054013 reaction equation
B(F)(F)F.[CH2:5]([O:12][C:13]([N:15]1[CH2:19][CH2:18][CH2:17][CH:16]1[CH2:20][C:21]1[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[O:23][C:22]=1[CH:30]=[CH:31][C:32](OCC)=[O:33])=[O:14])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.CC(C[AlH]CC(C)C)C.CCOC(C)=O>C(Cl)Cl>[CH2:5]([O:12][C:13]([N:15]1[CH2:19][CH2:18][CH2:17][CH:16]1[CH2:20][C:21]1[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[O:23][C:22]=1[CH:30]=[CH:31][CH2:32][OH:33])=[O:14])[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 6356Boron trifluorideHCID 8857Ethyl AcetateHCID 14487Diisobutylaluminum hydride2×HCID 67148751HCID 67148751, compound

Product 1

HCID 671480522-[2-(3-Hydroxy-propenyl)-benzofuran-3-ylmethyl]-pyrrolidine-1-carboxylic acid benzyl esterYield 72.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

At −78° C., BF3.etherate (0.6 mL, 4.8 mmol) was added to a solution containing 47 (1.7 g, 3.9 mmol) in anhydrous DCM (40 mL). After 10 min, DIBAL (1 M/DCM, 10 mL, 10 mmol) was added dropwise from an addition funnel. After 5 min following the complete addition of the DIBAL solution, EtOAc (10 mL) was added to quench the excess reagent. Dilute aqueous HCl was slowly added and the reaction mixture was allowed to slowly warm to ambient temperature. The product was extracted with DCM and EtOAc and the combined organic extracts were washed with dilute aqueous HCl, water, brine, dried over anhydrous Na2SO4, filtered and concentrated. The crude product was purified by flash silica gel chromatography (EtOAc/hexane, 1:2) to afford 1.1 g (72%) of 60 as a yellow-colored oil. 1H NMR (CDCl3, 300 MHz) δ7.65 & 7.03 (rotamer, d and app t, J=6.9, 7.8 Hz, 1H), 7.38 (m, 5H), 7.26-7.19 (m, 2H), 6.70-6.52 (m, 2H), 5.26-5.14 (m, 2H), 4.38 (m, 1H), 4.28 (m, 1H), 4.14 (m, 1H), 3.43 (m, 2H), 3.27 & 3.02 (rotamer, 2 m, 1H), 2.76-2.68 (m, 1H), 2.45 (m, 1H), 1.77-1.68 (m, 5H) ppm.

Workup

  1. customAt −78° C.
  2. additionetherate (0.6 mL, 4.8 mmol) was added to a solution
  3. waitAfter 5 min following
  4. additionwas added
  5. customto quench the excess reagent
  6. additionDilute aqueous HCl was slowly added
  7. extractionThe product was extracted with DCM and EtOAc
  8. washthe combined organic extracts were washed with dilute aqueous HCl, water, brine
  9. dry with materialdried over anhydrous Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude product was purified by flash silica gel chromatography (EtOAc/hexane, 1:2)

Sources & evidence

ORD record
ord-9e30b42a37dd4ce9900282cd9a74e3e6
Source dataset
uspto-grants-2016_07
Patent number
US09394249B2

Reaction notes

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