Reaction #168617

Reaction equation

N-ethylpiperidine

(2R,3S)-3-(trityl-amino)-pentan-2-ol

DMSO

oxalyl chloride

→

title compound

(3S)-3-(Trityl-amino)-pentan-2-one

Solvents

DCM

ether

hexane

DCM

DCM

Conditions

Workup

1. 1
   workup.STIRRINGwith stirring
2. 2
   workup.STIRRINGThe reaction mixture was stirred at this temperature for 4 h
3. 3
   Temperatureto warm to room temperature over 16 h
4. 4
   Washwashed with water (200 mL)
5. 5
   ExtractionThe aqueous phase was extracted with DCM (2×50 mL)
6. 6
   Washthe combined organic phase washed with brine (50 mL)
7. 7
   Dryingdried (MgSO4)
8. 8
   Otherevaporated in vacuo
9. 9
   workup.DISSOLUTIONThe residue was dissolved in Et2O (100 mL)
10. 10
    Otherthe solid precipitate removed by filtration
11. 11
    Otherthe filtrate was evaporated in vacuo
12. 12
    workup.DISSOLUTIONThe residue was dissolved in hexane (50 mL)
13. 13
    Otherthe solid precipitate removed by filtration
14. 14
    Otherthe filtrate was evaporated in vacuo

Procedure

To a stirred solution of DMSO (1.95 mL, 2.8 eq, 27.48 mmol) in DCM (30 mL) under an argon atmosphere at −45° C., was added oxalyl chloride (2 M in DCM, 6.85 mL, 1.4 eq, 13.70 mmol) dropwise. The reaction mixture was stirred at −45° C. for 1 h, after which time a solution (2R,3S)-3-(trityl-amino)-pentan-2-ol (3.39 g, 1 eq, 9.83 mmol) in DCM (20 mL) was added dropwise with stirring. The reaction mixture was stirred at this temperature for 4 h, when TLC (hexane:ether; 80:20) indicated that the reaction had gone to completion. To the reaction mixture was added N-ethylpiperidine (6.71 mL, 5 eq, 48.84 mmol), and the solution allowed to warm to room temperature over 16 h. The reaction mixture was diluted with more DCM (50 mL) and washed with water (200 mL). The aqueous phase was extracted with DCM (2×50 mL), and the combined organic phase washed with brine (50 mL), dried (MgSO4) and evaporated in vacuo. The residue was dissolved in Et2O (100 mL), the solid precipitate removed by filtration and the filtrate was evaporated in vacuo. The residue was dissolved in hexane (50 mL), the solid precipitate removed by filtration and the filtrate was evaporated in vacuo to afford the title compound as a light yellow oil. Yield: 3.15 g (93%). 1H-NMR (d6-DMSO, 250 MHz): δ 0.73 (t, 3H, J=7.50 Hz, —NHCH(CH2CH3)C(CH3)O), 1.45-1.62 (m, 5H, —NHCH(CH2CH3)C(CH3)O), 3.12 (d, 1H, J=8.53 Hz, —NHCH(CH2CH3)C(CH3)O), 3.31 (m, 1H, —NHCH(CH2CH3)C(CH3)O), 7.13-7.45 (m, 15H, 3×Ph).

Source