Ethyl 3,3-diethoxypropionate → Ethyl 2-(6-bromoisochroman-1-yl)acetate

HRID 368820Notes

Reaction equation

HRID 368820 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][OH:10])[CH:5]=[CH:6][CH:7]=1.[CH2:11]([O:13][CH:14]([O:21]CC)[CH2:15][C:16](OCC)=O)[CH3:12]>[N+](C)([O-])=O.[Ti](Cl)(Cl)(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:6][CH:7]=1)[CH:16]([CH2:15][C:14]([O:13][CH2:11][CH3:12])=[O:21])[O:10][CH2:9][CH2:8]2

Participants

5

Reactant 2

HCID 66389Ethyl 3,3-diethoxypropionateHCID 27340902-(3-Bromophenyl)ethan-1-ol

Product 1

HCID 10566032Ethyl 2-(6-bromoisochroman-1-yl)acetate

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6375NitromethaneSolvent

Procedure

Titanium tetrachloride (1M in methylene chloride, 51 ml) is added over a period of 10 min to an ice-cooled mixture of 2-(3-bromophenyl)ethanol (XLV, 4.34 g, 21.6 mmol) and ethyl 3,3-diethoxypropionate (LXXXV, 4.93 g, 25.9 mmol) in nitromethane (5 ml). After stirring for 10 min, the ice bath is removed and the mixture is allowed to stir at 20-25° for 5 hr, at which time it is poured onto ice/aqueous hydrochloric acid (~1N). The mixture is extracted with dichloromethane and backwashed with hydrochloric acid (0.5N)/saline and saline. The organic phase is separated dried over sodium sulfate, concentrated, and the residue chromatographed on silica gel eluting with ethyl acetate/hexane (5/95). The appropriate fractions are pooled and concentrated to give ethyl (6-bromoisochroman-1-yl)acetate (LXXVII), NMR (CDCl3) 1.28, 2.66-2.87, 2.96, 3.768, 3.807, 4.11, 4.21, 5.19, 6.93 and 7.28 δ.

Workup

  1. temperaturecooled
  2. customthe ice bath is removed
  3. stirringto stir at 20-25° for 5 hr, at which time it
  4. additionis poured onto ice/aqueous hydrochloric acid (~1N)
  5. extractionThe mixture is extracted with dichloromethane
  6. customThe organic phase is separated
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customthe residue chromatographed on silica gel eluting with ethyl acetate/hexane (5/95)
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-677f7ef40ccc453da19b66aa85879fe8
Source dataset
uspto-grants-2000_10
Patent number
US06133446

Reaction notes

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