Sodium hydride → 2-(3,5-Difluoro-2-nitro-phenyl)-malonic acid di-tert-butyl ester

HRID 1767013Notes

Reaction equation

HRID 1767013 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].F[C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([F:26])[C:20]=1[N+:27]([O-:29])=[O:28]>CN(C=O)C>[C:14]([O:13][C:3](=[O:12])[CH:4]([C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([F:26])[C:20]=1[N+:27]([O-:29])=[O:28])[C:5]([O:7][C:8]([CH3:9])([CH3:10])[CH3:11])=[O:6])([CH3:17])([CH3:16])[CH3:15]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 675671,3,5-Trifluoro-2-nitrobenzeneHCID 68324Di-tert-butyl malonate

Product 1

HCID 235418862-(3,5-Difluoro-2-nitro-phenyl)-malonic acid di-tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of NaH (54.6 g, 60%, 1.365 mol) in 600 mL of DMF was added di-t-Butyl malonate (118 g, 0.546 mol) at 0° C. and stirred for 30 min. 2,4,6 trifluoronitrobenzene was added as a solution in 400 mL of DMF (75 g, 0.42 mol) over 3 hours and the solution stirred at ambient temperature for 12 hours. The reaction mixture was extracted with ethyl acetate (3×'s). The ethyl acetate was washed with water (3×'s) and with brine and dried over MgSO4 and concentrated to give 62 g of crude product. LCMS [M+Na]−396; 1H NMR (500 MHz, DMSO) δ 7.81 (m, 1H), 7.27 (m, 1H), 5.00 (s, 1H), 1.41 (m, 18H).

Workup

  1. stirringthe solution stirred at ambient temperature for 12 hours
  2. extractionThe reaction mixture was extracted with ethyl acetate (3×'s)
  3. washThe ethyl acetate was washed with water (3×'s) and with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-0191054ee22d4e339cedba3578848370
Source dataset
uspto-grants-2007_06
Patent number
US07232826B2

Reaction notes

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