Methyl Acetate → HCID 56982112, compound

HRID 1604086Notes

Reaction equation

HRID 1604086 reaction equation
[C:1]([O:4][CH3:5])(=[O:3])[CH3:2].[Li+].CC([N-]C(C)C)C.CN(C)P(=O)(N(C)C)N(C)C.Br[CH2:26][C:27]([CH:29]([N:31]([CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH3:30])=[O:28]>C1COCC1>[CH3:5][O:4][C:1](=[O:3])[CH2:2][CH2:26][C:27](=[O:28])[C@@H:29]([N:31]([CH2:39][C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1)[CH2:32][C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[CH3:30]

Participants

6

Reactant 4

HCID 6584Methyl AcetateHCID 12679HexamethylphosphoramideHCID 2724682Lithium diisopropylamideHCID 19606958HCID 19606958, compound

Product 1

HCID 56982112HCID 56982112, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methyl acetate (1.0 mmol, 0.08 mL) was added dropwise to a solution of LDA (1.05 mmol) in 2.0 mL THF at -78° C., and the resulting solution was stirred for 45 minutes. Hexamethyl phosphoric triamide (1.0 mmol, 0.18 mL) was then added, and after 15 minutes a solution of α-(N,N-dibenzylamino)ethyl bromomethyl ketone (crude from the previous reaction, assumed to be 1.0 mmol) in 2.0 mL was added via syringe. The resulting solution was stirred at -78° C. for 45 minutes and then quenched with saturated solution of NaHCO3. After a work-up as described in Example 8, 0.39 g of crude product was obtained. The product was further purified by column chromatography on silica gel with 8:1 hexanes-ethyl acetate as the solvent system (Rf=0.33) to yield 0.21 g (62%) of methyl-(5S)-5-(N,N-dibenzylamino)-4-oxo-hexanoate as a colorless viscous oil. Analytical data: 1H NMR (300.15 MHz) δ 0.95 (d, J=6.6 Hz, 3H), 2.62-2.30 (m, 4H), 3.36 (q, J=6.2 Hz, 1H), 3.60 (ABq, δA =3.41, δB =3.82, J=13.5 Hz, 4H), 3.49 (s, 3H), 7.23-7.37 (m, 10H); 13C NMR 5.1, 38.9, 48.8, 51.4, 54.4, 57.5, 126.9, 128.2, 128.8, 129.2, 139.4, 170.4, 208.2.

Workup

  1. additionwas added via syringe
  2. stirringThe resulting solution was stirred at -78° C. for 45 minutes
  3. customquenched with saturated solution of NaHCO3
  4. custom0.39 g of crude product was obtained
  5. customThe product was further purified by column chromatography on silica gel with 8:1 hexanes-ethyl acetate as the solvent system (Rf=0.33)

Sources & evidence

ORD record
ord-32ad1b82c6b74bd5abe8203bf25b7676
Source dataset
uspto-grants-1999_11
Patent number
US05990341

Reaction notes

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