Diisopropylamine → Lithium diisopropylamide

HRID 2199852Notes

Reaction equation

HRID 2199852 reaction equation
[Li+:1].CCC[CH2-].[CH:6]([NH:9][CH:10]([CH3:12])[CH3:11])([CH3:8])[CH3:7].C([N-]C(C)C)(C)C.[Li+].[CH3:21][C:22]1[N:26]=[C:25]([CH3:27])[N:24]([C:28]2[N:33]=[C:32]([CH3:34])[N:31]=[C:30]([C@@H:35]3[CH2:37][C@H:36]3[C:38]([O:40]CC)=O)[CH:29]=2)[N:23]=1.[Cl:43][CH2:44]I>C1COCC1.CCOC(C)=O>[CH:6]([N-:9][CH:10]([CH3:12])[CH3:11])([CH3:8])[CH3:7].[Li+:1].[Cl:43][CH2:44][C:38]([C@H:36]1[CH2:37][C@@H:35]1[C:30]1[CH:29]=[C:28]([N:24]2[C:25]([CH3:27])=[N:26][C:22]([CH3:21])=[N:23]2)[N:33]=[C:32]([CH3:34])[N:31]=1)=[O:40]

Participants

9

Reactant 5

HCID 7912DiisopropylamineHCID 11644ChloroiodomethaneHCID 61028n-Butyl lithiumHCID 2724682Lithium diisopropylamideHCID 86732076ethyl trans-2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropanecarboxylate

Product 2

HCID 2724682Lithium diisopropylamideHCID 901570132-chloro-1-((1S,2S)-2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropyl)ethanone

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A 2 M solution of lithium diisopropylamide (LDA) was prepared by the addition of N-butyllithium (8.0 mL, 2.5 M, 20 mmol) to diisopropylamine (2.4 g, 24 mmol) in THF (2 mL) at 0° C. After stirring for 1 h, the LDA solution (6.6 mL, 13.2 mmol) was added to a flask containing 1-4 (1.0 g, 3.3 mmol) and chloroiodomethane (2.9 g, 17 mmol) in THF (33 mL) at −78° C. The mixture was stirred at −78° C. for 2 h then warmed to room temperature and diluted with EtOAc (30 mL). The solution was washed with saturated aqueous sodium bicarbonate (2×20 mL) and brine (1×20 mL) and the organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by silica gel chromatography (20-40% EtOAc/hexanes) to afford 1-5 as a white solid.

Workup

  1. stirringThe mixture was stirred at −78° C. for 2 h
  2. washThe solution was washed with saturated aqueous sodium bicarbonate (2×20 mL) and brine (1×20 mL)
  3. dry with materialthe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by silica gel chromatography (20-40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-6e3d48de0af2466180cbe069eb4bfb57
Source dataset
uspto-grants-2016_06
Patent number
US09359348B2

Reaction notes

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