Reaction #89730

Reaction equation

Lithium hexamethyldisilazide

1-benzyl 4-methyl(2S)-2-[benzyl((2R)-2-(1-ethoxyethoxy)-3-[(4-methylphenyl)sulfonyl]oxypropyl)amino]succinate

toluene

→

product

Yield 78.2%

2-benzyl 3-methyl(2S,3S,5S)-1-benzyl-5-(1-ethoxyethoxy)piperidine-2,3-dicarboxylate

Yield 78.2%

Solvents

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   Temperatureto warm up to at 0 Celsius gradually
2. 2
   workup.STIRRINGstirred at 0 Celsius for 30 min
3. 3
   OtherAfter quenched with aq ammonium chloride
4. 4
   Extractionthe mixture was extracted with ethyl acetate
5. 5
   WashThe combined organic layers were washed with water, brine
6. 6
   Dryingdried (sodium sulfate)
7. 7
   Concentrationconcentrated
8. 8
   Otherto dry
9. 9
   OtherThe residue was purified on silica gel column
10. 10
    Washeluting with 0 to 20% EtOAc in hexane

Procedure

To a solution of 1-benzyl 4-methyl(2S)-2-[benzyl((2R)-2-(1-ethoxyethoxy)-3-[(4-methylphenyl)sulfonyl]oxypropyl)amino]succinate (34.30 g, 0.05464 mol) in a mixture of tetrahydrofuran (90.0 mL, 1.11 mol) and toluene (470.0 mL, 4.412 mol) at −78 Celsius was added 1.00 M of Lithium hexamethyldisilazide in tetrahydrofuran (65.6 mL). The resulting mixture was stirred at −78 Celsius overnight, and then allowed to warm up to at 0 Celsius gradually and stirred at 0 Celsius for 30 min. After quenched with aq ammonium chloride, the mixture was extracted with ethyl acetate. The combined organic layers were washed with water, brine, and dried (sodium sulfate), and concentrated to dry. The residue was purified on silica gel column, eluting with 0 to 20% EtOAc in hexane, to yield the cyclized product (19.47 g, 78.2%). MS (ESI): (M+H)+=456.0.

Source