Carbon Dioxide → Lithium diisopropylamide

HRID 479125Notes

Reaction equation

HRID 479125 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:32])[CH2:17][N:18]=[C:19]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH3:14].Br[CH2:34][C:35]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:38]([O:45][CH2:46][CH2:47][C:48]2[N:49]=[C:50]([C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)[O:51][C:52]=2[CH3:53])=[CH:37][CH:36]=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:32])[CH:17]([N:18]=[C:19]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[CH2:34][C:35]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:38]([O:45][CH2:46][CH2:47][C:48]2[N:49]=[C:50]([C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)[O:51][C:52]=2[CH3:53])=[CH:37][CH:36]=1)[CH3:14]

Participants

9

Reactant 5

HCID 280Carbon DioxideHCID 7912DiisopropylamineHCID 319508Ethyl 2-(diphenylmethyleneamino)acetateHCID 180035404-[2-(4-Bromomethyl-naphthalen-1-yloxy)-ethyl]-5-methyl-2-phenyl-oxazoleHCID 178418339Butyllithium

Product 2

HCID 2724682Lithium diisopropylamideHCID 865874772-(Benzhydrylidene-amino)-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 2.0 ml nBuLi (1.5 M, hexane) to a solution of 0.324 g (3.2 mmol) of diisopropylamine in 6 ml of abs. THF at −10°. After cooling to −78°, 0.802 g of N-(diphenylmethylene)glycine ethyl ester (3.0 mmol), dissolved in 2 ml of abs. THF, was added dropwise and the mixture kept for 15 Min. at that temperature to ensure complete deprotonation. 0.81 g of crude 4-[2-(4-bromomethyl-naphthalen-1-yloxy)-ethyl]-5-methyl-2-phenyl-oxazole (<0.20 mmol, prepared as described above [example 7a] on a 2.06 mmol scale), dissolved in 12 ml of abs. THF, was then added, followed by 5 ml of DMPU. After stirring for 30 Min. at dry ice temperature and 90 Min. at 0°, the homogeneous reaction mixture was poured onto crashed ice/NH4Cl, extracted twice with AcOEt, washed with NH4Cl to pH 7, dried over sodium sulfate, and evaporated to dryness. Flash chromatography (SiO2, hexane/AcOEt=8/2) yielded 0.829 g of the title compound as colorless, sticky oil.

Workup

  1. customat −10°
  2. temperatureAfter cooling to −78°
  3. dissolutiondissolved in 12 ml of abs
  4. additionat 0°, the homogeneous reaction mixture was poured
  5. extractionextracted twice with AcOEt
  6. washwashed with NH4Cl to pH 7
  7. dry with materialdried over sodium sulfate
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-04de30bd336d4902b5427364eb450223
Source dataset
uspto-grants-2003_11
Patent number
US06642389B2

Reaction notes

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