Diethyl Oxalate → Ethyl 2-[2-[(tert-butoxycarbonyl)amino]-5-chloro-4-methylphenyl]-2-oxoacetate

HRID 1243320Notes

Reaction equation

HRID 1243320 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:4][C:3]=1[CH3:16].C([Li])(C)(C)C.[C:22](OCC)(=[O:28])[C:23]([O:25][CH2:26][CH3:27])=[O:24].[NH4+].[Cl-]>CCOCC.CCCCC.C1COCC1>[C:11]([O:10][C:9]([NH:8][C:5]1[CH:4]=[C:3]([CH3:16])[C:2]([Cl:1])=[CH:7][C:6]=1[C:22](=[O:28])[C:23]([O:25][CH2:26][CH3:27])=[O:24])=[O:15])([CH3:12])([CH3:13])[CH3:14]

Participants

8

Reactant 4

HCID 7268Diethyl OxalateHCID 25517Ammonium ChlorideHCID 21905898tert-Butyl (4-chloro-3-methylphenyl)carbamateHCID 178418306HCID 178418306, compound

Product 1

HCID 21925406Ethyl 2-[2-[(tert-butoxycarbonyl)amino]-5-chloro-4-methylphenyl]-2-oxoacetateYield 95.9%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

A solution of 5.9 g of tert-butyl 4-chloro-3-methylphenylcarbamate in 60 ml of ether is cooled to −50° C., under a nitrogen atmosphere, 42 ml of a solution of tert-butyllithium in pentane are added dropwise, and the mixture is stirred for 2 hours while allowing the temperature to rise to −20° C. The reaction mixture is cooled to −70° C., a solution of 4.5 g of diethyl oxalate in 30 ml of THF is added dropwise and the resulting mixture is stirred for 1 hour while allowing the temperature to return to 20° C. The reaction mixture is poured into saturated NH4Cl solution, the phases are separated by settling, the aqueous phase is extracted with EtOAc, the combined organic phases are washed with 1N HCl and dried over Na2SO4, and the solvent is evaporated off under vacuum. The residue is chromatographed on silica gel, eluting with an iso ether/pentane mixture (50/50; v/v). 8 g of the expected product are obtained in the form of an oil which crystallizes, m.p.=111° C.

Workup

  1. customto rise to −20° C
  2. stirringthe resulting mixture is stirred for 1 hour
  3. customto return to 20° C
  4. customthe phases are separated
  5. extractionthe aqueous phase is extracted with EtOAc
  6. washthe combined organic phases are washed with 1N HCl
  7. dry with materialdried over Na2SO4
  8. customthe solvent is evaporated off under vacuum
  9. customThe residue is chromatographed on silica gel
  10. washeluting with an iso ether/pentane mixture (50/50; v/v)

Sources & evidence

ORD record
ord-1dde900aa8b44abf9f06166bb84c8f83
Source dataset
uspto-grants-2006_10
Patent number
US07119086B2

Reaction notes

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