Carbon Dioxide → Lithium diisopropylamide

HRID 479120Notes

Reaction equation

HRID 479120 reaction equation
[Li:1]CCCC.[CH:6]([NH:9][CH:10]([CH3:12])[CH3:11])([CH3:8])[CH3:7].[CH2:13]([O:15][C:16](=[O:20])[CH2:17][O:18][CH3:19])[CH3:14].Br[CH2:22][C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]([O:33][CH2:34][CH2:35][C:36]2[N:37]=[C:38]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[O:39][C:40]=2[CH3:41])=[CH:25][CH:24]=1.C(=O)=O>CN1C(=O)N(C)CCC1.C1COCC1>[Li+:1].[CH3:7][CH:6]([N-:9][CH:10]([CH3:12])[CH3:11])[CH3:8].[CH2:13]([O:15][C:16](=[O:20])[CH:17]([O:18][CH3:19])[CH2:22][C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]([O:33][CH2:34][CH2:35][C:36]2[N:37]=[C:38]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[O:39][C:40]=2[CH3:41])=[CH:25][CH:24]=1)[CH3:14]

Participants

9

Reactant 5

HCID 280Carbon DioxideHCID 7912DiisopropylamineHCID 77544Ethyl 2-methoxyacetateHCID 180035404-[2-(4-Bromomethyl-naphthalen-1-yloxy)-ethyl]-5-methyl-2-phenyl-oxazoleHCID 178418339Butyllithium

Product 2

HCID 2724682Lithium diisopropylamideHCID 695574422-Methoxy-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-naphthalen-1-yl}-propionic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Procedure

LDA was prepared by adding via syringe 1.0 ml nBuLi (1.5 M, hexane) to a solution of 0.162 g (1.6 mmol) of diisopropylamine in 3 ml of abs. THF at −5°. After cooling to −78°, 0.177 g of methoxyacetic acid ethyl ester (1.50 mmol), dissolved in 1 ml of abs. THF, was added and the mixture kept for 15 Min. at that temperature to ensure complete deprotonation. 0.38 g of crude 4-[2-(4-bromomethyl-naphthalen-1-yloxy)-ethyl]-5-methyl-2-phenyl-oxazole (<0.90 mmol, prepared as described above on a 1 mmol scale), dissolved in 6 ml of abs. THF, was then added, followed by 3 ml of DMPU. After stirring for 15 Min. at dry ice temperature and 30 Min. at 0°, the reaction mixture was poured onto crashed ice, extracted twice with AcOEt, washed with water, dried over sodium sulfate, and evaporated to dryness. Twofold flash chromatography (SiO2, hexane/AcOEt=74/26, then 76/24) yielded 0.145 g of the title compound as colorless oil.

Workup

  1. customat −5°
  2. temperatureAfter cooling to −78°
  3. dissolutiondissolved in 6 ml of abs
  4. additionat 0°, the reaction mixture was poured
  5. extractionextracted twice with AcOEt
  6. washwashed with water
  7. dry with materialdried over sodium sulfate
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-ff7bff95f0064aba9e4ecd23e4ab4905
Source dataset
uspto-grants-2003_11
Patent number
US06642389B2

Reaction notes

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