Tetrahydrofuran → HCID 69601012, compound

HRID 2215089Notes

Reaction equation

HRID 2215089 reaction equation
O[CH2:2][C@H:3]1[CH2:7][S:6][C:5](=[O:8])[N:4]1[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]#[N:16].CC(OI1(OC(C)=O)(OC(C)=O)O[C:28](=O)[C:27]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]1=2)=O.[H-].[Na+].C1C[O:44][CH2:43][CH2:42]1>C(Cl)Cl>[O:8]=[C:5]1[N:4]([CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]#[N:16])[C@@H:3](/[CH:2]=[CH:42]/[C:43](=[O:44])[CH2:28][C:27]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:7][S:6]1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 159087TriacetoxyperiodinaneHCID 69600972HCID 69600972, compound

Product 1

HCID 69601012HCID 69601012, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-2 (0.65 g, 2.7 mmol) in 15 mL CH2Cl2 was added Dess Martin periodinane (1.4 g, 3.2 mmol) portion wise and the resulting solution was stirred for 2 hours. The solution was concentrated in vacuo, to which toluene was added and concentrated thrice to remove acetic acid. The concentrate was then filtered through celite with CH2Cl2 and concentrated in vacuo. The crude product was then diluted in 7 mL of THF and added to a solution of the Wittig reagent dimethyl 2-oxo-3-phenylpropylphosphonate (1.3 g, 5.3 mmol) and 60% sodium hydride (0.2 g, 5.1 mmol) in 7 mL of THF at 0° C. which had been premixed 30 minutes. The reaction mixture was stirred for 15 minutes at the initial temperature and was allowed to warm up to room temperature for 1 hour. The solution was stored at 4° C. overnight, quenched with saturated aqueous ammonium chloride solution and was extracted with ethyl acetate. The organic phases were then combined, and sequentially washed with H2O, brine and dried over Na2SO4, filtered and concentrated in vacuo. The compound was purified by flash chromatography using 40% ethyl acetate/hexanes to yield 350 mg of 4-3 as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.37–7.20 (m, 5H), 6.74 (dd, 1H), 6.31 (d, 1H), 4.34 (q, 1H), 3.88 (s, 2H), 3.54–3.44 (m, 2H), 3.01 (dd, 1H), 2.77 (m, 1H), 2.33 (t, 2H), 1.67–1.60 (m, 2H), 1.47–1.30 (m, 4H), 1.28–1.23 (m, 2H); MS (+ESI): m/z 356.9 (M+1)+.

Workup

  1. concentrationThe solution was concentrated in vacuo, to which toluene
  2. additionwas added
  3. concentrationconcentrated thrice
  4. customto remove acetic acid
  5. filtrationThe concentrate was then filtered through celite with CH2Cl2
  6. concentrationconcentrated in vacuo
  7. additionThe crude product was then diluted in 7 mL of THF
  8. additionhad been premixed 30 minutes
  9. stirringThe reaction mixture was stirred for 15 minutes at the initial temperature
  10. waitThe solution was stored at 4° C. overnight
  11. customquenched with saturated aqueous ammonium chloride solution
  12. extractionwas extracted with ethyl acetate
  13. washsequentially washed with H2O, brine
  14. dry with materialdried over Na2SO4
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo
  17. customThe compound was purified by flash chromatography

Sources & evidence

ORD record
ord-1351d27f1d6c4727ad030b85f5c5a7e9
Source dataset
uspto-grants-2006_09
Patent number
US07109223B2

Reaction notes

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