Diisopropylamine → HCID 20456494, compound

HRID 1263042Notes

Reaction equation

HRID 1263042 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[N:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19].N1C=CC=CC=1C[Li].[C:28]([NH:38][C:39]1[C:40](=[CH:45][CH:46]=[CH:47][CH:48]=1)C(OC)=O)(=[O:37])[C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=1.C1C[O:52][CH2:51]C1>CCCCCC.CO.C(Cl)Cl.O.C(O)(=O)C>[N:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH2:19][C:51]([C:34]1[CH:33]=[C:32]([O:35][CH3:36])[CH:31]=[CH:30][C:29]=1[C:28]([NH:38][C:39]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:40]=1)=[O:37])=[O:52]

Participants

12

Reactant 6

HCID 7912DiisopropylamineHCID 79752-MethylpyridineHCID 8028TetrahydrofuranHCID 779930HCID 779930, compoundHCID 178418339ButyllithiumHCID 178506852HCID 178506852, compound

Product 1

HCID 20456494HCID 20456494, compound

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8058HexaneSolvent

Conditions

Temperature
10 °C

Procedure

A dry, nitrogen purged flask was charged with 1.875 mL 1.6 N (3.0 mole) n-butyl lithium in hexane. The solution was stirred under nitrogen and chilled to -45° to -40° C., and 1.5 L THF (dried over molecular sieve 4 A) was added slowly. Diisopropylamine (303.6 g; 3.0 mole) was added at such a rate that the temperature did not exceed -30° C. Then 307.3 g (3.3 mole) 2-picoline was added with stirring, keeping the temperature below -30° C. The cooling was interrupted, and the mixture was slowly warmed to 10° C. by which time the conversion to anion was complete and all the 2-picolyl lithium had redissolved. The solution was recooled to -45° to -40° C. (the orange solid reprecipitated), and a solution of 285.3 g (1.0 mole) methyl N-p-anisoylanthranilate (III) in 1.9 L THF was added at a rate so the temperature did not exceed -30° C. After the addition, the mixture was slowly warmed to 25° C. The solution was adjusted to pH 6 with 500 mL acetic acid; 5.0 L H2O was added with stirring. Then the organic solvents were distilled in vacuo and the residual yellow semi-solid product was extracted with CH2Cl2 (1×2.5 L). The extract was washed with H2O (1×1.0 L) and stripped to dryness in vacuo. The residue was dissolved in 6.7 L boiling isopropanol. The solution was chilled with stirring to 5°±5° C., and the resulting yellow solid was collected on a filter, rinsed with isopropanol and dried in vacuo at 80° C. for six hours. The filtrate was concentrated and chilled to yield a second crop of product. Both crops of intensely yellow material exhibited single spots in the TLC (7.5 cm silica gel with indicator, 9 CH2Cl2 :1 methanol, UV). The total yield was 306.7 g (88.5%) of material, m.p. 145°-148.5° C.

Workup

  1. temperaturechilled to -45° to -40° C.
  2. dry with material1.5 L THF (dried over molecular sieve 4 A)
  3. additionwas added slowly
  4. customdid not exceed -30° C
  5. stirringwith stirring
  6. customthe temperature below -30° C
  7. customwas recooled to -45° to -40° C.
  8. additionwas added at a rate so the temperature
  9. customdid not exceed -30° C
  10. additionAfter the addition
  11. temperaturethe mixture was slowly warmed to 25° C
  12. stirringwith stirring
  13. distillationThen the organic solvents were distilled in vacuo
  14. extractionthe residual yellow semi-solid product was extracted with CH2Cl2 (1×2.5 L)
  15. washThe extract was washed with H2O (1×1.0 L)
  16. dissolutionThe residue was dissolved in 6.7 L
  17. temperatureThe solution was chilled
  18. stirringwith stirring to 5°±5° C.
  19. customthe resulting yellow solid was collected on a filter
  20. washrinsed with isopropanol
  21. customdried in vacuo at 80° C. for six hours
  22. concentrationThe filtrate was concentrated
  23. temperaturechilled
  24. customto yield a second crop of product

Sources & evidence

ORD record
ord-8013c9d5660244e28a617075a2d673b7
Source dataset
uspto-grants-1984_06
Patent number
US04454324

Reaction notes

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