Triethylamine → (S)-ethyl 1-(3-methylbutanoyl)piperidine-3-carboxylate

HRID 1483944Notes

Reaction equation

HRID 1483944 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][C@H:3]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:2]1.CCN(CC)CC.[C:19](Cl)(=[O:24])[CH2:20][CH:21]([CH3:23])[CH3:22]>C(Cl)Cl>[CH3:22][CH:21]([CH3:23])[CH2:20][C:19]([N:1]1[CH2:6][CH2:5][CH2:4][C@H:3]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:2]1)=[O:24]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 66054Isovaleryl chlorideHCID 187784Ethyl (3S)-piperidine-3-carboxylate

Product 1

HCID 81344202(S)-ethyl 1-(3-methylbutanoyl)piperidine-3-carboxylateYield 97.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Ethyl (S)-Piperidine-3-carboxylate (25 g, 159.02 mmol) in anhydrous DCM (500 mL) was cooled down to 0° C. and treated with Et3N. A solution of isovaleryl chloride (23.27 mL, 190.08 mmol, 1.2 eq.) in anhydrous DCM (200 mL) was added dropwise at 0° C. The resulting reaction mixture was kept on the cooling bath and allowed to warm up slowly to room temperature. After 6 hrs the reaction was washed subsequently with aqueous HCl solution (2M), saturated NaHCO3, brine, dried over Na2SO4, filtered, concentrated under vacuum and purified by filtration over a short silica gel column using EtOAc as solvent. The solvent was removed under vacuum to yield the desired product as pale yellow oil (37.4 g, 154.97 mmol, 97.5%) that was used in the next step without further purification. 1H NMR (400 MHz, DMSO-d6, 20° C.) δ 0.88 (pseudo d, J=6.4 Hz, 6H), 1.13-1.23 (m, 3H), 1.26-1.45 (m, 1H), 1.47-1.75 (m, 2H), 1.82-2.03 (m, 2H), 2.10-2.28 (m, 2H), 2.28-2.39 (m, 0.5H), 2.45-2.56 (m, 0.5H), 2.84 (dd, J=10.0, 12.8 Hz, 0.5H), 2.97-3.11 (m, 1H), 3.38 (dd, J=8.8, 13.6 Hz, 0.5H), 3.63-3.83 (m, 1.5H), 4.00-4.14 (m, 2H), 4.26-4.36 (dm, 0.5H). MS 242 (MH).

Workup

  1. customThe resulting reaction mixture
  2. washAfter 6 hrs the reaction was washed subsequently with aqueous HCl solution (2M), saturated NaHCO3, brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. filtrationpurified by filtration over a short silica gel column
  7. customThe solvent was removed under vacuum

Sources & evidence

ORD record
ord-c5445014b9314108ab1c326bc0c146a7
Source dataset
uspto-grants-2016_08
Patent number
US09420814B2

Reaction notes

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