Water → HCID 14418356, compound

HRID 1793964Notes

Reaction equation

HRID 1793964 reaction equation
[C:1]([O:8][CH3:9])(=[O:7])[CH2:2][C:3]([O:5][CH3:6])=[O:4].[H-].[Na+].BrC[C:14]1[C:15]([C:20]#[N:21])=[CH:16][CH:17]=[CH:18][CH:19]=1.O.[CH2:23]1COCC1>>[CH3:6][O:5][C:3](=[O:4])[CH:2]([CH2:23][C:18]1[CH:19]=[CH:14][C:15]([C:20]#[N:21])=[CH:16][CH:17]=1)[C:1]([O:8][CH3:9])=[O:7]

Participants

6

Reactant 5

HCID 962WaterHCID 7943Dimethyl malonateHCID 8028Tetrahydrofuran2×HCID 24758Sodium hydrideHCID 895992-(Bromomethyl)benzonitrile

Product 1

HCID 14418356HCID 14418356, compoundYield 45%

Conditions

Temperature
80 °C

Procedure

Dimethyl malonate (10.00 g, 75.7 mmol) was added to a suspension of NaH (60% in oil, 3.33 g, 83.3 mmol) in THF (100 mL) over 20 minutes at room temperature. The mixture was heated at 80° C. for 15 minutes, then a solution of α-bromotolunitrile (14.84 g, 75.69 mmol) in THF (100 mL) was added. Heating was continued at 80° C. for 1 hour, then at 50° C. for 64 hours. Water (30 mL) was added, and the aqueous phase was extracted with EtOAc (3×20 mL). The combined organic phases were dried (MgSO4) and concentrated. Purification of the crude material on silica gel (25% EtOAc/hexanes) gave the title compound as colourless crystals (8.49 g, 45%). 1H NMR (CDCl3) δ 3.27 (d, 2H, J=9.0 Hz), 3.67 (t, 1H, J=9.0 Hz), 3.70 (s, 6H), 7.32 (d, 2H, J=9.0 Hz), 7.58 (d, 2H, J=9.0 Hz).

Workup

  1. temperatureHeating
  2. waitat 50° C. for 64 hours
  3. extractionthe aqueous phase was extracted with EtOAc (3×20 mL)
  4. dry with materialThe combined organic phases were dried (MgSO4)
  5. concentrationconcentrated
  6. customPurification of the crude material on silica gel (25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-46d22e07c0f1425991c37abb8656cc44
Source dataset
uspto-grants-2006_04
Patent number
US07022717B2

Reaction notes

Loading…