m-Chlorophenethylic alcohol → 6-Chloro-1-(2-chloroethyl)isochroman

HRID 368822

Reaction equation

HRID 368822 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[CH2:5][CH2:6][OH:7].C(O[CH:14](OCC)[CH2:15][CH2:16][Cl:17])C>[Ti](Cl)(Cl)(Cl)Cl.[N+](C)([O-])=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH:14]([CH2:15][CH2:16][Cl:17])[O:7][CH2:6][CH2:5]2

Participants

5

Reactant 2

HCID 78856m-Chlorophenethylic alcoholHCID 962173-Chloro-1,1-diethoxypropane

Product 1

HCID 232887876-Chloro-1-(2-chloroethyl)isochroman

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6375NitromethaneSolvent

Procedure

A mixture of 3-chlorophenethyl alcohol (XLV, 5.9055 g, 0.0398 mol), 3-chloropropionaldehyde diethyl acetal (LXII, 7.2 ml, 0.0430 mol) and nitromethane (3 ml) is cooled in an ice/water bath. Titanium tetrachloride (1M in dichloromethane, 88 ml, 0.088 mol) is added dropwise and the mixture is heated at 45° for 3 hr. After cooling, the mixture is poured onto ice/aqueous hydrochloric acid (1N) and extracted with dichloromethane. The combined organic layers are backwashed with hydrochloric acid (1N) and filtered through a pad of Celite topped with sodium sulfate. The filtrate is concentrated and chromatographed twice on silica gel eluting with ethyl acetate/hexane (5/95). The appropriate fractions are pooled and concentrated to give 6-chloro-1-(2-chloroethyl)isochroman (LXIV), NMR (CDCl3) 2.23, 2.70, 2.93, 3.75, 4.09, 4.89, 7.01 and 7.16 δ.

Workup

  1. temperatureis cooled in an ice/water bath
  2. temperaturethe mixture is heated at 45° for 3 hr
  3. temperatureAfter cooling
  4. additionthe mixture is poured onto ice/aqueous hydrochloric acid (1N)
  5. extractionextracted with dichloromethane
  6. filtrationfiltered through a pad of Celite
  7. concentrationThe filtrate is concentrated
  8. customchromatographed twice on silica gel eluting with ethyl acetate/hexane (5/95)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-9ac4074b32ba48118f125bcc5d0e4963
Source dataset
uspto-grants-2000_10
Patent number
US06133446

Linked notes

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