Water → di-tert-Butyl (3-bromo-4-cyanophenyl)malonate

HRID 1519530Notes

Reaction equation

HRID 1519530 reaction equation
[H-].[Na+].[C:3]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])(=[O:12])[CH2:4][C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].[Br:18][C:19]1[CH:26]=[C:25](F)[CH:24]=[CH:23][C:20]=1[C:21]#[N:22].O>CN(C=O)C>[C:14]([O:13][C:3](=[O:12])[CH:4]([C:25]1[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[C:19]([Br:18])[CH:26]=1)[C:5]([O:7][C:8]([CH3:9])([CH3:10])[CH3:11])=[O:6])([CH3:17])([CH3:16])[CH3:15]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 68324Di-tert-butyl malonateHCID 1189392-Bromo-4-fluorobenzonitrile

Product 1

HCID 67517893di-tert-Butyl (3-bromo-4-cyanophenyl)malonate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of NaH (0.37 g, 15.4 mmol, 60.0% dispersion in oil) in DMF (40 mL) was added a solution of di-t-butyl malonate (3.6 g, 16 mmol) in DMF (10 mL) at 0° C. and this was stirred for 15 minutes. Subsequently, 2-bromo-4-fluorobenzonitrile (3.0 g, 15.0 mmol) was added in one portion and the reaction mixture was stirred for 8 hours at 80° C. and three hours at room temperature. Water (50 mL) was added and the aqueous layer was extracted with EtOAc (2×100 mL). The combined organic extracts were washed with water (50 mL) and brine (50 mL), dried over MgSO4 and filtered. After evaporation in vacuo, the residue was purified by flash chromatography (20% EtOAc in hexane) to give di-tert-Butyl(3-bromo-4-cyanophenyl)malonate as a light brown solid. 1H NMR (500 MHz, DMSO-d6) δ 7.97 (d, J=8 Hz, 1H), 7.88 (s, 1H), 7.60 (d, J=8 Hz, 1H), 4.95 (s, 1H), 1.42 (s, 18H). LC-MS (IE, m/z): 398 [M+1]+.

Workup

  1. stirringthe reaction mixture was stirred for 8 hours at 80° C. and three hours at room temperature
  2. extractionthe aqueous layer was extracted with EtOAc (2×100 mL)
  3. washThe combined organic extracts were washed with water (50 mL) and brine (50 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customAfter evaporation in vacuo
  7. customthe residue was purified by flash chromatography (20% EtOAc in hexane)

Sources & evidence

ORD record
ord-3af559153b2a4ed1a447ace08b58c29a
Source dataset
uspto-grants-2015_07
Patent number
US09073882B2

Reaction notes

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