Reaction #89717

Reaction equation

Lithium hexamethyldisilazide

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

toluene

→

product

Yield 69.9%

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

Yield 69.9%

Solvents

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   Temperatureto warm up to −20 Celsius
2. 2
   workup.STIRRINGstirred at −20 Celsius for 3 h
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 brine
6. 6
   Otherdried
7. 7
   Concentrationconcentrated
8. 8
   Otherto dry
9. 9
   Washeluting with 0 to 20% EtOAc in hexane

Procedure

To a solution of 1-benzyl 4-methyl(2S)-2-[benzyl((2S)-2-(1-ethoxyethoxy)-3-[(4-methylphenyl)sulfonyl]oxypropyl)amino]succinate (35.7 g, 0.0569 mol) in a mixture of tetrahydrofuran (95.5 mL, 1.18 mol) and toluene (490 mL, 4.6 mol) at −78 Celsius was was added 1.00 M of Lithium hexamethyldisilazide in tetrahydrofuran (68.2 mL). The reaction was stirred at −78 Celsius overnight then allowed to warm up to −20 Celsius and stirred at −20 Celsius for 3 h. After quenched with aq ammonium chloride, the mixture was extracted with ethyl acetate. The combined organic layers were washed with brine, dried and concentrated to dry. The residue was applied on silica gel column, eluting with 0 to 20% EtOAc in hexane, to afford the product (18.1 g, 69.9%). MS (ESI): (M+H)+=456.2. The corresponding diastereoisomer was also obtained (4.52 g, 17.5%).

Source