Diethyl Malonate → HCID 118101242, compound

HRID 708849Notes

Reaction equation

HRID 708849 reaction equation
Br[C:2]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][C:3]=1[CH2:4][N:5]([CH3:16])[C:6](=[O:15])[O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.N1CCC[C@H]1C(O)=O.C(=O)([O-])[O-].[Cs+].[Cs+].[C:38]([O:46][CH2:47][CH3:48])(=[O:45])[CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41]>CS(C)=O.[Cu]I>[CH2:8]([O:7][C:6]([N:5]([CH2:4][C:3]1[CH:17]=[C:18]([N+:21]([O-:23])=[O:22])[CH:19]=[CH:20][C:2]=1[CH:39]([C:40]([O:42][CH2:43][CH3:44])=[O:41])[C:38]([O:46][CH2:47][CH3:48])=[O:45])[CH3:16])=[O:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

7

Reactant 4

HCID 7761Diethyl MalonateHCID 10796Cesium carbonateHCID 145742L-ProlineHCID 66744764HCID 66744764, compound

Product 1

HCID 118101242HCID 118101242, compoundYield 73.6%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
50 °C

Procedure

Benzyl 2-bromo-5-nitrobenzyl(methyl)carbamate (3.000 g, 7.91 mmol), copper(i) iodide (0.301 g, 1.582 mmol), L-proline (0.364 g, 3.16 mmol) and cesium carbonate (5.16 g, 15.82 mmol) were mixed in a pressure vial and degassed (3×). A solution of diethyl malonate (1.501 mL, 9.89 mmol) in DMSO (10 mL) was added, the reaction mixture was degassed again and stirred at 50° C. for 3 days. The cooled reaction mixture was partitioned between EtOAc (100 mL) and NH4Cl (aq. std.; 100 mL). The organic layer was washed with brine (2×50 mL) and dried (Na2SO4). EtOAc was removed under reduced pressure and the residue was purified by flash chromatography (0-40% EtOAc/hexane). Fractions were combined and concentrated under reduced pressure to give 15A (2.668 g, 5.82 mmol, 73.6% yield) as a colorless syrup. MS (ESI) m/z: 459.2 [M+1]+. 1H NMR: (400 MHz, CDCl3) δ ppm 8.18 (1H, d, J=8.53 Hz), 8.09 (1H, br. s.), 7.72 (1H, d, J=7.28 Hz), 7.36 (5H, d, J=15.81 Hz), 5.20 (3H, br. s.), 4.67 (2H, br. s.), 4.07-4.28 (4H, m), 2.81 (3H, s), 1.24 (6H, t, J=7.15 Hz).

Workup

  1. customdegassed (3×)
  2. customthe reaction mixture was degassed again
  3. customThe cooled reaction mixture
  4. customwas partitioned between EtOAc (100 mL) and NH4Cl (aq. std.; 100 mL)
  5. washThe organic layer was washed with brine (2×50 mL)
  6. dry with materialdried (Na2SO4)
  7. customEtOAc was removed under reduced pressure
  8. customthe residue was purified by flash chromatography (0-40% EtOAc/hexane)
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-68d32af942474155b648abddb62e471c
Source dataset
uspto-grants-2015_11
Patent number
US09174974B2

Reaction notes

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