Methyl 2-bromobenzoate → Methyl 2-[3-(3-hydroxyphenyl)-3-oxopropyl]benzoate

HRID 2259527Notes

Reaction equation

HRID 2259527 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[Li+].[Cl-].[Li]O[C:16]([CH3:18])=[O:17].[OH2:19]>CN(C=O)C.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[OH:17][C:16]1[CH:18]=[C:11]([C:10](=[O:19])[CH2:9][CH2:8][C:2]2[CH:11]=[CH:10][CH:9]=[CH:8][C:3]=2[C:4]([O:6][CH3:7])=[O:5])[CH:2]=[CH:3][CH:4]=1

Participants

7

Reactant 3

HCID 11894Methyl 2-bromobenzoateHCID 433294Lithium ChlorideHCID 178526219lithium;acetate;hydrate

Product 1

HCID 10564983Methyl 2-[3-(3-hydroxyphenyl)-3-oxopropyl]benzoate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a suspension of 3-(7-chloroquinolin-2-yl)methoxy)benzaldehyde (10.08 g, 33.9 mmol; U.S. Pat. No. 4,851,409 example 16 step 1) in toluene at 0° C. was added dropwise 1M vinylmagnesium bromide in THF (37 mL). After 30 min. the solution was quenched with NH4OAc, extracted with H2O, brine and dried over Na2SO4. The solvent was removed to afford 11.07 g of the allylic alcohol. This alcohol (11.00 g, 32.4 mmol), methyl o-bromobenzoate (7.31 g, 34 mmol), Pd(OAc)2 (218 mg), LiCl (1.37 g) and LiOAc.H2O (9.04 g) in 65 mL of DMF were heated to 100° C. for 3 h. The solution was cooled, poured in H2O (300 mL) and extracted with EtOAc (3×200 mL). The organic fractions were combined, washed with H2O, brine and dried over Na2SO4. Purification by chromatography (5% EtOAc in toluene) yield 12.44 g of LVIII. 1H NMR (300 MHz, CD3COCD3) δ3.30 (4H, m), 3.75 (3H, s), 5.45 (2H, s), 7.30-8.00 (12H, m) and 8.40 (1H, d).

Workup

  1. temperatureThe solution was cooled
  2. extractionextracted with EtOAc (3×200 mL)
  3. washwashed with H2O, brine
  4. dry with materialdried over Na2SO4
  5. customPurification by chromatography (5% EtOAc in toluene) yield 12.44 g of LVIII

Sources & evidence

ORD record
ord-2aba68ae29cd423c91c8d14d686056ab
Source dataset
uspto-grants-1995_12
Patent number
US05472964

Reaction notes

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