Piperidine → (R)-1-Benzyl 3-ethyl piperidine-1,3-dicarboxylate

HRID 48471Notes

Reaction equation

HRID 48471 reaction equation
[C:1]([O-:4])([O-:3])=O.[K+].[K+].[NH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1.[C:13](Cl)([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14].[CH2:24]1COC[CH2:25]1.O>>[CH2:24]([O:3][C:1]([C@@H:9]1[CH2:10][CH2:11][CH2:12][N:7]([C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])[CH2:8]1)=[O:4])[CH3:25]

Participants

5

Reactant 4

HCID 8082PiperidineHCID 10387Benzyl chloroformate2×HCID 11430Potassium CarbonateHCID 21881883Oxolane--water (1/1)

Product 1

HCID 16091193(R)-1-Benzyl 3-ethyl piperidine-1,3-dicarboxylateYield 100%

Conditions

Temperature
0 °C

Procedure

A 1.0 L round-bottom flask was charged with K2CO3 (29.2 g; 171 mmol), piperidine (50 g; 163 mmol), and a 1:1 mixture of THF/H2O (800 mL). A 150 mL addition funnel was placed on the flask and charged with CbzCl (29.2 g, 171 mmol). The flask was cooled to 0° C. and then CbzCl was added dropwise over 5 minutes. The reaction mixture was warmed to 20° C. and stirred for 1 h. The reaction mixture was extracted with EtOAc (500 mL) and the organic layer was washed with water (500 mL), saturated NaCl (500 mL), dried (MgSO4), filtered and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, hexanes/EtOAc 9:1 to 4:1) to give pure product (49.3 g, 100% yield). 1H-NMR (300 MHz) δ (ppm) 7.40 (m; 5H); 5.17 (s; 2H); 4.19 (q; 2H); 4.04 (m; 1H); 3.12 (m; 1H); 2.95 (m; 1H); 2.48 (m; 1H); 2.08 (m; 1H); 1.75 (m; 3H); 1.53 (m; 1H); 1.28 (t; 3H).

Workup

  1. additionA 150 mL addition funnel
  2. temperatureThe reaction mixture was warmed to 20° C.
  3. extractionThe reaction mixture was extracted with EtOAc (500 mL)
  4. washthe organic layer was washed with water (500 mL), saturated NaCl (500 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by flash chromatography (silica gel, hexanes/EtOAc 9:1 to 4:1)

Sources & evidence

ORD record
ord-57c4a33a5941471eb1ea80f6f62fc050
Source dataset
uspto-grants-2004_03
Patent number
US06703508B2

Reaction notes

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