Dimethyl Sulfoxide → 1,2-Dibenzyl 3-(tert-butyl) (2S,3S)-5-oxopiperidine-1,2,3-tricarboxylate

HRID 1477376Notes

Reaction equation

HRID 1477376 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[OH:11][CH:12]1[CH2:17][N:16]([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[C@H:15]([C:28]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:29])[C@@H:14]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:13]1.C(N(CC)CC)C>C(Cl)Cl.C(OCC)(=O)C>[O:11]=[C:12]1[CH2:17][N:16]([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[C@H:15]([C:28]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:29])[C@@H:14]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:13]1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 576924231,2-Dibenzyl 3-(tert-butyl) (2S,3S)-5-hydroxypiperidine-1,2,3-tricarboxylate

Product 1

HCID 593051041,2-Dibenzyl 3-(tert-butyl) (2S,3S)-5-oxopiperidine-1,2,3-tricarboxylateYield 63.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent4×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
78 °C

Procedure

To a cooled solution of oxalyl chloride (315 mg) in methylene chloride (2.5 mL) was added dropwise a solution of DMSO (0.30 mL) in methylene chloride (3.0 mL) at 78° C. The mixture was stirred at 78° C. for 30 min, 1,2-dibenzyl 3-tert-butyl(2S,3S)-5-hydroxypiperidine-1,2,3-tricarboxylate of step 1m (900 mg) in methylene chloride (4 mL) was added dropwise. The mixture was stirred at 78° C. to 60° C. for 1 h. Triethylamine (620 mg) in methylene chloride (2.5 mL) was added. The mixture was allowed to warm to RT during a period of 2 h. The mixture was diluted with ethyl acetate (75 mL) and washed with brine (2×25 mL). The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The residue was flash chromatographed on silica gel column to afford 1,2-dibenzyl 3-tert-butyl(2S,3S)-5-oxopiperidine-1,2,3-tricarboxylate (570 mg). MS (ESI): 490.3 (M+Na+); 368.2 (M+H+—COO(t-Bu)).

Workup

  1. stirringThe mixture was stirred at 78° C. to 60° C. for 1 h
  2. temperatureto warm to RT during a period of 2 h
  3. washwashed with brine (2×25 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customchromatographed on silica gel column

Sources & evidence

ORD record
ord-6f42cc17c157476fa8b55b4eb1c6cd78
Source dataset
uspto-grants-2016_08
Patent number
US09403775B2

Reaction notes

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