Dimethyl malonate → HCID 86700878, compound

HRID 881772Notes

Reaction equation

HRID 881772 reaction equation
[C:1]([O:8][CH3:9])(=[O:7])[CH2:2][C:3]([O:5][CH3:6])=[O:4].[H-].[Na+].[Br:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]23[O:25][C:22]([CH2:26]I)([CH2:23][CH2:24]2)[CH2:21][CH2:20]3)=[CH:15][CH:14]=1>CC(N(C)C)=O>[Br:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]23[O:25][C:22]([CH2:3][CH2:2][C:1]([O:8][CH3:9])=[O:7])([CH2:23][CH2:24]2)[CH2:21][CH2:20]3)=[CH:15][CH:14]=1.[Br:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]23[O:25][C:22]([CH2:26][CH:2]([C:1]([O:8][CH3:9])=[O:7])[C:3]([O:5][CH3:6])=[O:4])([CH2:23][CH2:24]2)[CH2:21][CH2:20]3)=[CH:15][CH:14]=1

Participants

6

Reactant 3

HCID 7943Dimethyl malonateHCID 24758Sodium hydrideHCID 86700879HCID 86700879, compound

Product 2

HCID 86700877HCID 86700877, compoundYield 28%HCID 86700878HCID 86700878, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of dimethyl malonate (0.47 mL, 4.1 mmol) in anhydrous dimethyl acetamide (5.6 mL) cooled in an ice-water bath was added NaH (60% dispersion in mineral oil, 163 mg, 4.1 mmol) portion-wise and the reaction was let stir at rt for 30 min until homogeneous. To this was added 1-(4-bromophenyl)-4-(iodomethyl)-7-oxabicyclo[2.2.1]heptane (440 mg, 1.12 mmol) and the reaction was stirred in a microwave reactor at 150° C. for 45 min. The resulting yellow reaction mixture was quenched with a saturated aqueous NH4Cl solution and extracted with EtOAc. The organic phase was dried over MgSO4, filtered and concentrated by rotary evaporation in vacuo to afford a crude yellow oil. Purification of the crude material by column chromatography (40 g silica gel, 0-30% EtOAc:Hept, monitor 225 nm) afforded 108 mg (28%) of methyl 3-(4-(4-bromophenyl)-7-oxabicyclo[2.2.1]heptan-1-yl)propanoate (decarboxylated material) as a clear yellow film and 245 mg (55%) of the title compound as a clear yellow film. 1H NMR (400 MHz, DMSO-d6): δ ppm 1.54-1.79 (m, 6H), 2.06-2.16 (m, 2H), 2.39 (d, J=7.1 Hz, 2H), 3.66 (s, 6H), 3.73 (t, J=7.1 Hz, 1H), 7.27 (d, J=8.6 Hz, 2H), 7.54 (d, J=8.6 Hz, 2H). ESI-MS m/z: 399.0 [M+H]+, retention time 1.59 min (condition E).

Workup

  1. stirringthe reaction was stirred in a microwave reactor at 150° C. for 45 min
  2. customThe resulting yellow reaction mixture was quenched with a saturated aqueous NH4Cl solution
  3. extractionextracted with EtOAc
  4. dry with materialThe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporation in vacuo
  7. customto afford a crude yellow oil
  8. customPurification of the crude material by column chromatography (40 g silica gel, 0-30% EtOAc:Hept, monitor 225 nm)

Sources & evidence

ORD record
ord-efc312b7b12a43d984b38d561a50c3a9
Source dataset
uspto-grants-2015_03
Patent number
US08993619B2

Reaction notes

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