Nitrogen → Lithium diisopropylamide

HRID 1383178Notes

Reaction equation

HRID 1383178 reaction equation
[Li:1]CCCC.[CH:6]([NH:9][CH:10]([CH3:12])[CH3:11])([CH3:8])[CH3:7].[CH:13](=[N:20][C@H:21]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH3:22])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.I[CH2:29][CH2:30][O:31][CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][O:33]1.N#N>CN(P(N(C)C)(N(C)C)=O)C.C1COCC1>[CH:6]([N-:9][CH:10]([CH3:12])[CH3:11])([CH3:8])[CH3:7].[Li+:1].[CH:13](=[N:20][C:21]([CH3:22])([CH2:29][CH2:30][O:31][CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][O:33]1)[C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

9

Reactant 5

HCID 947NitrogenHCID 7912DiisopropylamineHCID 10560169HCID 10560169, compoundHCID 111186622H-Pyran, tetrahydro-2-(2-iodoethoxy)-HCID 178418339Butyllithium

Product 2

HCID 2724682Lithium diisopropylamideHCID 15599313HCID 15599313, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 12679HexamethylphosphoramideSolvent

Procedure

A solution of lithium diisopropylamide was prepared by dropwise addition of n-BuLi (Aldrich 1.6M in hexane, 228 mL, 0.365 mol) to a solution of diisopropylamine (Aldrich, 51.6 g, 0.51 mol) in a mixture of dry THF (700 mL) and dry HMPA (Aldrich, 40 mL) kept at 30°-40°. The solution was then cooled to -70° and a solution of ethyl N-benzylidene-l-alaninate 10A, 74.9 g, 0.365 mol) was added dropwise to the solution allowing the reaction mixture warm to -20° for several min. The resulting red solution was then cooled to -70°. 2-(2-Iodoethoxy)tetrahydro-2-H-pyran (10B, 98.1 g, 0.383 mol) was then added to the solution at such a rate that the temperature in the reaction mixture did not rise above -65°. The solution was allowed to warm slowly to RT and stirred for 14 h. The volume of the solution was reduced to 300 mL by a stream of dry N2 during the last few hours to facilitate the final workup. The reaction was quenched with satd. NaCl (800 mL) and diluted with Et2O (800 mL). The Et2O was removed and the aqueous layer extracted with hexane (500 mL). The Et2O and hexane layers were combined and dried (Na2SO4). The solution was filtered and the solvent removed to give 124 g of of crude red oil. Bulb to bulb distillation (in 1% aq. NEt3 washed glassware) (210° bath temperature/0.3 mm) gave 95 g of ethyl 2-benzylideneamino-2-methyl-4-((tetrahydro-2Hpyran-2-yl)oxy)butyrate which was homogeneous by vpc and gave acceptable NMR and mass spectra. It was stored under N2 in the refrigerator and was used without further purification.

Workup

  1. customkept at 30°-40°
  2. temperatureThe solution was then cooled to -70°
  3. temperaturewarm to -20° for several min
  4. temperatureThe resulting red solution was then cooled to -70°
  5. customdid not rise above -65°
  6. customThe reaction was quenched with satd
  7. additionNaCl (800 mL) and diluted with Et2O (800 mL)
  8. customThe Et2O was removed
  9. extractionthe aqueous layer extracted with hexane (500 mL)
  10. dry with materialdried (Na2SO4)
  11. filtrationThe solution was filtered
  12. customthe solvent removed
  13. customto give 124 g of of crude red oil
  14. distillationBulb to bulb distillation (in 1% aq. NEt3 washed glassware) (210° bath temperature/0.3 mm)

Sources & evidence

ORD record
ord-60e956b8324f4d65980109e8202911a3
Source dataset
uspto-grants-1989_02
Patent number
US04808632

Reaction notes

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