Diisopropylamine → Lithium diisopropylamide

HRID 394275

Reaction equation

HRID 394275 reaction equation
[Li:1]CCCC.[CH:6]([NH:9][CH:10]([CH3:12])[CH3:11])([CH3:8])[CH3:7].[C:13]([O:16][CH2:17][CH3:18])(=[O:15])[CH3:14].I[CH2:20][C:21]1[N:22]=[C:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[S:24][CH:25]=1>CN1CCCN(C)C1=O.C1COCC1>[Li+:1].[CH3:7][CH:6]([N-:9][CH:10]([CH3:12])[CH3:11])[CH3:8].[CH2:17]([O:16][C:13](=[O:15])[CH2:14][CH2:20][C:21]1[N:22]=[C:23]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[S:24][CH:25]=1)[CH3:18]

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 8857Ethyl AcetateHCID 131965984-(Iodomethyl)-2-phenylthiazoleHCID 178418339Butyllithium

Product 2

HCID 2724682Lithium diisopropylamideHCID 686166683-(2-Phenyl-thiazol-4-yl)-propionic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Conditions

Temperature
-78 °C

Procedure

LDA was prepared by adding 4.7 ml of n-BuLi (1.6 M, hexane) to a solution of 0.76 g (7.5 mmol) of diisopropylamine in 3 ml of abs. THF at −5° C. Then, the mixture was cooled to −78° C., 0.77 g (8.74 mmol) of ethyl acetate were added and the mixture was kept for 15 minutes at that temperature to ensure complete deprotonation. Afterwards, 0.79 g (2.5 mmol) of 4-iodomethyl-2-phenyl-thiazole dissolved in 5 ml of abs. THF and 3 ml of 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinon (DMPU) were added and stirring was continued for 0.5 hours at −78° C. Then, the reaction mixture was quenched with ammonium chloride solution, extracted twice with AcOEt, washed with water, dried over anhydrous sodium sulfate, and evaporated to dryness. The residue was chromatographed on silicagel with dichloromethane as eluent. 0.46 g of 3-(2-phenyl-thiazol-4-yl)-propionic acid ethyl ester were obtained as light yellow liquid (70% of theory).

Workup

  1. customat −5° C
  2. waitwas continued for 0.5 hours at −78° C
  3. customThen, the reaction mixture was quenched with ammonium chloride solution
  4. extractionextracted twice with AcOEt
  5. washwashed with water
  6. dry with materialdried over anhydrous sodium sulfate
  7. customevaporated to dryness
  8. customThe residue was chromatographed on silicagel with dichloromethane as eluent

Sources & evidence

ORD record
ord-4651043e0a9f4b7fb5abe05bc419df7a
Source dataset
uspto-grants-2004_10
Patent number
US06809110B2

Linked notes

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