Tetrahydrofuran → HCID 69267908, compound

HRID 494536Notes

Reaction equation

HRID 494536 reaction equation
[CH2:1]([O:8][C:9](=[O:18])[CH:10]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].O1[CH2:33][CH2:32][CH2:31][CH2:30]1>>[CH3:11][C:10]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([CH2:30]/[CH:31]=[CH:32]/[CH2:33][C:2]([CH3:7])([CH3:3])[CH3:1])[C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:18]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 2733832Lithium HexamethyldisilazideHCID 14494047HCID 14494047, compound

Product 1

HCID 69267908HCID 69267908, compoundYield 72%

Conditions

Temperature
-78 °C

Procedure

A solution of 2-phenyl-propionic acid benzyl ester (3.15 g, 13.1 mmol) in tetrahydrofuran (25 mL) at −78° C. was treated dropwise with a lithium hexamethyldisilazide solution (14.4 mL, IM in tetrahydrofuran, 14.4 mmol) and stirred for 30 minutes at −78° C. Example 35B (3.26 g, 17.0 mmol) was added to the solution and the reaction was allowed to warm to 25° C. and stirred for an additional 4 hours. The solvent was removed in vacuo and the residue was partitioned between water and ethyl acetate. The aqueous phase was extracted three times with ethyl acetate and the ethyl acetate layers were combined, washed with a saturated sodium bicarbonate solution, dried with sodium sulfate, filtered, and concentrated in vacuo. The residue was chromatographed on silica gel eluting with hexane, then 5% ethyl acetate in hexane, and 10% ethyl acetate in hexane to give the title compound (3.32 g, 72%). 1H NMR (300 MHz, CDCl3): δ ppm 0.80 (m, 9 H) 1.53 (m, 3 H) 1.79 (m, 2H) 2.63 (m, 1 H) 2.82 (m, 1 H) 5.10 (m, 2 H) 5.18 (m, 1 H) 5.47 (m, 1 H) 7.27 (m, 10 H). MS (ESI+) m/z 368 (M+NH4)+.

Workup

  1. temperatureto warm to 25° C.
  2. stirringstirred for an additional 4 hours
  3. customThe solvent was removed in vacuo
  4. customthe residue was partitioned between water and ethyl acetate
  5. extractionThe aqueous phase was extracted three times with ethyl acetate
  6. washwashed with a saturated sodium bicarbonate solution
  7. dry with materialdried with sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was chromatographed on silica gel eluting with hexane

Sources & evidence

ORD record
ord-d2f889298705420eb0b4438df5899804
Source dataset
uspto-grants-2009_05
Patent number
US07538105B2

Reaction notes

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