2-Phenylethanol → ethyl 3,4-dihydro-1H-2-benzopyran-1-acetate

HRID 368842Notes

Reaction equation

HRID 368842 reaction equation
[CH2:1]([OH:9])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:10]([O:12][CH:13]([O:20]CC)[CH2:14][C:15](OCC)=O)[CH3:11]>[Ti](Cl)(Cl)(Cl)Cl.[N+](C)([O-])=O>[CH:15]1([CH2:14][C:13]([O:12][CH2:10][CH3:11])=[O:20])[C:8]2[C:3](=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:2][CH2:1][O:9]1

Participants

5

Reactant 2

HCID 60542-PhenylethanolHCID 66389Ethyl 3,3-diethoxypropionate

Product 1

HCID 10822798ethyl 3,4-dihydro-1H-2-benzopyran-1-acetate

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6375NitromethaneSolvent

Procedure

Titanium tetrachloride (1M in methylene chloride, 90 ml, 90.0 mmol) is added over a period of 20 minutes to an ice-cooled mixture of phenethyl alcohol (XLV, 4.9 ml, 41.0 mmol), ethyl 3,3-diethoxypropionate (LXXV, 9.1 ml, 46.8 mmol) and nitromethane (17 ml). The mixture is stirred for 2 hr and then concentrated, diluted with ether, poured into ice/hydrochloric acid (1N), and allowed to stir. The phases are separated and the aqueous phase is extracted three times with ether. The combined organic phases are backwashed with saline, dried over magnesium sulfate and concentrated. The residue is chromatographed on silica gel eluting with ethyl acetate/hexane (10/90). The appropriate fractions are pooled and concentrated to give ethyl (±)-(isochroman-1-yl)acetate (LXXVII), NMR (CDCl3) 1.28, 2.68-3.04, 3.82, 4.13, 4.22, 5.26, 7.05 and 7.16 δ.

Workup

  1. temperaturecooled
  2. concentrationconcentrated
  3. additiondiluted with ether
  4. additionpoured into ice/hydrochloric acid (1N)
  5. stirringto stir
  6. customThe phases are separated
  7. extractionthe aqueous phase is extracted three times with ether
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated
  10. customThe residue is chromatographed on silica gel eluting with ethyl acetate/hexane (10/90)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-b5c2f26e53234191932eecb750729a72
Source dataset
uspto-grants-2000_10
Patent number
US06133446

Reaction notes

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