Hydrochloric Acid → Diethyl (6-methoxy-1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)(methyl)propanedioate

HRID 709843Notes

Reaction equation

HRID 709843 reaction equation
[H-].[Na+].[CH3:3][CH:4]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:5]([O:7][CH2:8][CH3:9])=[O:6].Br[CH:16]1[CH2:25][CH2:24][C:23]2[C:18](=[CH:19][CH:20]=[C:21]([O:26][CH3:27])[CH:22]=2)[C:17]1=[O:28].Cl>CN(C=O)C>[CH3:3][C:4]([CH:16]1[CH2:25][CH2:24][C:23]2[C:18](=[CH:19][CH:20]=[C:21]([O:26][CH3:27])[CH:22]=2)[C:17]1=[O:28])([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:10]([O:12][CH2:13][CH3:14])=[O:11]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11857Diethyl methylmalonateHCID 24758Sodium hydrideHCID 116012912-bromo-6-methoxy-3,4-dihydronaphthalen-1(2H)-one

Product 1

HCID 46194820Diethyl (6-methoxy-1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)(methyl)propanedioateYield 83.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 6 L of ice cold DMF was added 183 grams of NaH; the mixture stirred and a solution of 811.2 grams diethyl methylmalonate in 1.5 L DMF was added dropwise. The temp was kept at 0-5° C. for 2 hrs, and then cooled below −3° C., and 650 grams bromo-6-methoxy-3,4-dihydronaphthalen-1(2H)-one was added. The reaction was followed by HPLC until the starting material disappeared. The mixture was poured onto ice water, adjusted to pH 4-5 with HCl, and extracted with ethyl acetate. The organic layer was washed with brine, dried, decolorized and concentrated. To the residue was added ether, the mixture cooled, filtered, and the residue washed with petroleum ether to get 745 g of diethyl 2-methyl-2-(6-methoxy-1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)malonate, M=348.2, purity 96.57%.

Workup

  1. temperaturecooled below −3° C.
  2. additionThe mixture was poured onto ice water
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. customdried
  6. concentrationconcentrated
  7. additionTo the residue was added ether
  8. temperaturethe mixture cooled
  9. filtrationfiltered
  10. washthe residue washed with petroleum ether

Sources & evidence

ORD record
ord-ffacad8ceecd49f0aaf72ff8264fa5e2
Source dataset
uspto-grants-2015_11
Patent number
US09181191B2

Reaction notes

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