Methyl chloroformate → HCID 21251110, compound

HRID 1275643Notes

Reaction equation

HRID 1275643 reaction equation
[CH3:1][O:2][C:3]1[C:8]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:7][CH:6]=[C:5]([O:17][CH3:18])[N:4]=1.CN(CCN(C)C)C.C([Li])CCC.Cl[C:33]([O:35][CH3:36])=[O:34]>CCOCC>[C:33]([C:7]1[CH:6]=[C:5]([O:17][CH3:18])[N:4]=[C:3]([O:2][CH3:1])[C:8]=1[NH:9][C:10](=[O:16])[O:11][C:12]([CH3:14])([CH3:15])[CH3:13])([O:35][CH3:36])=[O:34]

Participants

6

Reactant 4

HCID 6586Methyl chloroformateHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 10977999Tert-butyl 2,6-dimethoxy-3-pyridinylcarbamateHCID 178418339Butyllithium

Product 1

HCID 21251110HCID 21251110, compoundYield 34.5%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-78 °C

Procedure

The product of Example 27 (1 g, 3.93 mmol) was dissolved in Et2O (35 mL) and TMEDA (1.7 mL, 1.18 mmol) and cooled to -78° C. n-Butyllithium (4.75 mL, 11.87 mmol) was added dropwise and the reaction was allowed to stir for 15 minutes at -78° C. before warming to -10° C. for 2.5 hours. The solution was cooled back to -78° C. and methyl chloroformate (0.6 mL, 7.8 mmol) dissolved in Et2O (4.5 mL) was added dropwise. The reaction was held at -78° C. for 10 minutes and then warmed to -10° C. and allowed to stir for 1.5 hours before quenching with NH4Cl (sat). The reaction mixture was extracted 3× with EtOAc. The organics were combined, washed with brine, dried over MgSO4, concentrated in vacuo. The residue was purified by column chromatography using hexane/ethyl acetate as eluant (gradient 9/1 to 4/1) to provide 0.423 g (34%) of tert-butyl N-(4-carbomethoxy-2,6-dimethoxy-3-pyridyl)carbamate as a white solid. Electrospray Mass Spec: 312.8 (M+H)+.

Workup

  1. additionwas added dropwise
  2. temperaturebefore warming to -10° C. for 2.5 hours
  3. temperatureThe solution was cooled back to -78° C.
  4. additionwas added dropwise
  5. waitThe reaction was held at -78° C. for 10 minutes
  6. temperaturewarmed to -10° C.
  7. stirringto stir for 1.5 hours
  8. custombefore quenching with NH4Cl (sat)
  9. extractionThe reaction mixture was extracted 3× with EtOAc
  10. washwashed with brine
  11. dry with materialdried over MgSO4
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-0b51b4fb08bc41f2b045428ace382d34
Source dataset
uspto-grants-2000_12
Patent number
US06162821

Reaction notes

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