Ethyl diethoxyacetate → methyl 5-bromo-3,4-dihydro-1H-isochromene-1-carboxylate

HRID 2173263Notes

Reaction equation

HRID 2173263 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][OH:10].[CH2:11]([O:13][CH:14]([O:20]CC)[C:15](OCC)=O)C>C[N+]([O-])=O.Cl[Ti](Cl)(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]2[C:3]=1[CH2:8][CH2:9][O:10][CH:15]2[C:14]([O:13][CH3:11])=[O:20]

Participants

5

Reactant 2

HCID 80169Ethyl diethoxyacetateHCID 27340892-(2-Bromophenyl)ethan-1-ol

Product 1

HCID 66646338methyl 5-bromo-3,4-dihydro-1H-isochromene-1-carboxylate

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6375NitromethaneSolvent

Procedure

TiCl4 (76 g, 0.4 mol) was added over a period of 10 min to an ice-cooled mixture of 2-(2-bromophenyl)ethanol (20 g, 0.1 mol) and ethyl bis(ethyloxy)acetate (21.1 g, 0.120 mol) in 120 mL of CH3NO2. After stirring for 10 min, the ice bath was removed and the mixture was allowed to stire at room temperature overnight. The mixture was poured into ice/aqueous 1N HCl. Extracted with DCM and backwashed with 1HCl and brine, dried over anhydrous sodium sulfate and concentrated. The residue was purified with silica gel chromatography to give the product methyl 5-bromo-3,4-dihydro-1H-isochromene-1-carboxylate. 1H-NMR (400 MHz, CDCl3) δ 7.42˜7.47 (m, 1H), 7.29 (d, J=8.0 Hz, 1H), 7.02 (t, J=8.0 Hz, 1H), 5.22 (s, 1H), 4.16˜4.26 (m, 3H), 3.95˜4.01 (m, 1H), 3.46˜3.63 (m, 1H), 2.99˜3.03 (m, 1H), 1.24 (t, J=8.0 Hz, 3H).

Workup

  1. temperaturecooled
  2. customthe ice bath was removed
  3. waitto stire at room temperature overnight
  4. additionThe mixture was poured into ice/aqueous 1N HCl
  5. extractionExtracted with DCM
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified with silica gel chromatography

Sources & evidence

ORD record
ord-45b55b2f36294deb8c33d3541a2959b2
Source dataset
uspto-grants-2015_06
Patent number
US09056859B2

Reaction notes

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