Sodium hydride → 2-Cyano-2-(1-isopropyl-butyl)succinic acid 4-tert-butyl ester 1-methyl ester

HRID 1167945Notes

Reaction equation

HRID 1167945 reaction equation
[CH3:1][O:2][C:3](=[O:14])[CH:4]([C:12]#[N:13])[CH:5]([CH:9]([CH3:11])[CH3:10])[CH2:6][CH2:7][CH3:8].[H-].[Na+].Br[CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20]>C1COCC1>[CH3:1][O:2][C:3](=[O:14])[C:4]([C:12]#[N:13])([CH:5]([CH:9]([CH3:11])[CH3:10])[CH2:6][CH2:7][CH3:8])[CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 541521852-Cyano-3-isopropyl-hexanoic acid methyl ester

Product 1

HCID 538735702-Cyano-2-(1-isopropyl-butyl)succinic acid 4-tert-butyl ester 1-methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2-cyano-3-isopropyl-hexanoic acid methyl ester (1.9 g, 9.6 mmol) in 10 mL of THF is added to a slurry of NaH (washed with hexane, 0.23 g, 9.6 mmol) in 20 mL of THF which is cooled in an ice water bath under argon. The solution is stirred for 10 minutes, and t-butyl bromoacetate (2.1 g, 10.6 mmol) is added. The solution is warmed to room temperature. After 12 hours, the reaction is quenched by addition of 50 mL of saturated KH2PO4 and the THF is evaporated. The organic products are extracted into Et2O (3×50 mL), and the combined organic layers are dried over MgSO4. The solvent is evaporated, and the remaining oil is chromatographed under medium pressure over silica gel in 25% hexane/CH2Cl2. Yield of 2-cyano-2-(1-isopropyl-butyl)-succinic acid 4-tert-butyl ester 1-methyl ester=1.3 g (42%) as an oil.

Workup

  1. temperatureis cooled in an ice water bath under argon
  2. waitAfter 12 hours
  3. customthe reaction is quenched by addition of 50 mL of saturated KH2PO4
  4. customthe THF is evaporated
  5. extractionThe organic products are extracted into Et2O (3×50 mL)
  6. dry with materialthe combined organic layers are dried over MgSO4
  7. customThe solvent is evaporated
  8. customthe remaining oil is chromatographed under medium pressure over silica gel in 25% hexane/CH2Cl2

Sources & evidence

ORD record
ord-18817ad0d1f44a0cb310030094fd4f25
Source dataset
uspto-grants-2003_09
Patent number
US06620829B2

Reaction notes

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