Sodium hydride → Di-tert-butyl [4-(1,3-dioxolan-2-yl)-3-fluorophenyl]malonate

HRID 500661Notes

Reaction equation

HRID 500661 reaction equation
[C:1]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])(=[O:10])[CH2:2][C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].[H-].[Na+].Br[C:19]1[CH:24]=[CH:23][C:22]([CH:25]2[O:29][CH2:28][CH2:27][O:26]2)=[C:21]([F:30])[CH:20]=1.[NH4+].[Cl-]>C1COCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[O:26]1[CH2:27][CH2:28][O:29][CH:25]1[C:22]1[CH:23]=[CH:24][C:19]([CH:2]([C:3]([O:5][C:6]([CH3:7])([CH3:8])[CH3:9])=[O:4])[C:1]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[CH:20][C:21]=1[F:30]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 68324Di-tert-butyl malonateHCID 219386012-(4-Bromo-2-Fluorophenyl)-1,3-Dioxolane

Product 1

HCID 57443964Di-tert-butyl [4-(1,3-dioxolan-2-yl)-3-fluorophenyl]malonateYield 79%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

Ditert-butyl malonate (1.95 g, 9.02 mmol) was dissolved in THF (8 mL) and sodium hydride (60% dispersion in mineral oil, 0.36 g, 9.00 mmol) was added. The mixture was stirred for 10 minutes before adding Pd(PtBu3)2 (0.17 g, 0.333 mmol) and a solution of 2-(4-bromo-2-fluorophenyl)-1,3-dioxolane (2.03 g, 8.22 mmol) in THF (16 mL). The resulting mixture was heated to reflux under N2 for 18 hours. Room temperature was attained, saturated NH4Cl (150 mL) was added and the products extracted into EtOAc (125 mL). The organic extracts were dried over MgSO4 and concentrated in vacuo. Purification of the residue by MPLC gave 2.47 g of desired product (pale yellow oil, 79%). 1H NNR (CDCl3) δ 7.50 (t, J=8.1 Hz, 1H), 7.16 (m, 2H), 6.07 (s, 1H), 4.40 (s, 1H), 4.13 (m, 2H), 4.03 (m, 2H), 1.45 (s, 18H).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux under N2 for 18 hours
  3. customRoom temperature
  4. extractionthe products extracted into EtOAc (125 mL)
  5. dry with materialThe organic extracts were dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by MPLC

Sources & evidence

ORD record
ord-37e44df604e340e09c2108daaae6834b
Source dataset
uspto-grants-2010_08
Patent number
US07772238B2

Reaction notes

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