Acetoxyacetyl chloride → 3-[2-((R)-6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl]-oxazolidine-2,4-dione

HRID 251871Notes

Reaction equation

HRID 251871 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH2:8][N:7]([CH3:13])[CH2:6][C@H:5]2[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[NH2:20].C[Si](C)(C)[N-][Si](C)(C)C.[Na+].[C:31]([O:34][CH2:35][C:36](Cl)=[O:37])(=[O:33])C>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH2:8][N:7]([CH3:13])[CH2:6][C@H:5]2[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[N:20]1[C:36](=[O:37])[CH2:35][O:34][C:31]1=[O:33]

Participants

5

Reactant 3

HCID 26297Acetoxyacetyl chlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 66864574(R)-2-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamine

Product 1

HCID 117180843-[2-((R)-6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl]-oxazolidine-2,4-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(R)-2-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamine (300 mg, enantiomer B, preparation as described in WO2004085404) was dissolved in absolute THF (10 ml) and admixed at room temperature with stirring with sodium hexamethyl-disilazide solution (0.5 ml; 2 M in THF). After 30 min, acetoxyacetyl chloride (77 μl) was added and the mixture was stirred at room temperature for 2 h. Subsequently, the reaction mixture was concentrated, the residue was dissolved in ethyl acetate/water and basified with sodium hydrogencarbonate solution, and the phases were separated. The aqueous phase was extracted three times with ethyl acetate. The combined extracts were dried over magnesium sulfate, filtered and concentrated. 380 mg of the desired product were obtained. 40 mg thereof were dissolved in acetonitrile/water, acidified with 0.1 N hydrochloric acid and freeze-dried.

Workup

  1. customadmixed at room temperature
  2. concentrationSubsequently, the reaction mixture was concentrated
  3. dissolutionthe residue was dissolved in ethyl acetate/water
  4. customthe phases were separated
  5. extractionThe aqueous phase was extracted three times with ethyl acetate
  6. dry with materialThe combined extracts were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-59808eeaed50428bb904d24a5874807b
Source dataset
uspto-grants-2011_01
Patent number
US07868003B2

Reaction notes

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