Diisopropylamine → Lithium diisopropylamide

HRID 2215209

Reaction equation

HRID 2215209 reaction equation
[CH:1]([NH:4][CH:5]([CH3:7])[CH3:6])([CH3:3])[CH3:2].[Li:8]CCCC.[CH:13]([O:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])([CH3:15])[CH3:14].[CH:23]1([C:29]2[O:30][C:31]([CH3:47])=[C:32]([CH2:34][CH2:35][O:36][C:37]3[C:44]([CH3:45])=[CH:43][C:40]([CH:41]=[O:42])=[CH:39][C:38]=3[CH3:46])[N:33]=2)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1>C1COCC1>[Li+:8].[CH3:2][CH:1]([N-:4][CH:5]([CH3:7])[CH3:6])[CH3:3].[CH2:21]([O:20][C:18](=[O:19])[CH:17]([O:16][CH:13]([CH3:15])[CH3:14])[CH:41]([C:40]1[CH:43]=[C:44]([CH3:45])[C:37]([O:36][CH2:35][CH2:34][C:32]2[N:33]=[C:29]([CH:23]3[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]3)[O:30][C:31]=2[CH3:47])=[C:38]([CH3:46])[CH:39]=1)[OH:42])[CH3:22]

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 537908Ethyl isopropoxyacetateHCID 219496594-[2-(2-Cyclohexyl-5-methyl-oxazol-4-yl)-ethoxy]-3,5-dimethyl-benzaldehydeHCID 178418339Butyllithium

Product 2

HCID 2724682Lithium diisopropylamideHCID 694896663-{4-[2-(2-Cyclohexyl-5-methyl-oxazol-4-yl)-ethoxy]-3,5-dimethyl-phenyl}-3-hydroxy-2-isopropoxy-propionic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Procedure

LDA-solution in THF was prepared according to standard procedure from 0.162 g of diisopropylamine (1.60 mmol) and 1.00 ml of 1.5 M nBuLi (hexane) in 3 ml of abs. THF at −10°. After cooling to −78°, 0.219 g of ethyl isopropoxyacetate (1.50 mmol), dissolved in 0.8 ml of THF, was added and stirring continued for 30 Min. to complete enolate formation. 0.169 g of the above prepared 4-[2-(2-cyclohexyl-5-methyl-oxazol-4-yl)-ethoxy]-3,5-dimethyl-benzaldehyde (0.495 mmol), dissolved in 2 ml of THF, was then added at −78° and the mixture kept for 10 Min. at this temperature. Pouring onto crashed ice/NH4Cl, twofold extraction with AcOEt, washing with water, drying over sodium sulfate, and evaporation of the solvents, followed by flash chromatography (SiO2, hexane/AcOEt=65/35) afforded 0.191 g of the title compound (syn/anti-isomers) as colorless, sticky oil.

Workup

  1. customat −10°
  2. temperatureAfter cooling to −78°
  3. additionwas added
  4. additionwas then added at −78°
  5. additionPouring
  6. extractionice/NH4Cl, twofold extraction with AcOEt
  7. washwashing with water
  8. dry with materialdrying over sodium sulfate, and evaporation of the solvents

Sources & evidence

ORD record
ord-b8cba8c9187f4d8c8ed3166df09dcbec
Source dataset
uspto-grants-2006_09
Patent number
US07109225B2

Linked notes

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