Triethylamine → benzyl (2S,5S)-5-hydroxy-2-methylpiperidine-1-carboxylate

HRID 1749368Notes

Reaction equation

HRID 1749368 reaction equation
Cl.[CH3:2][C@@H:3]1[NH:8][CH2:7][C@@H:6]([OH:9])[CH2:5][CH2:4]1.C(N(CC)CC)C.[C:17](Cl)([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18]>C(Cl)Cl>[OH:9][C@@H:6]1[CH2:7][N:8]([C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[C@@H:3]([CH3:2])[CH2:4][CH2:5]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10387Benzyl chloroformateHCID 86681862rac-(3R,6R)-6-methylpiperidin-3-ol hydrochloride

Product 1

HCID 86724498benzyl (2S,5S)-5-hydroxy-2-methylpiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of ±trans-6-methylpiperidin-3-ol hydrochloride (14.0 g, 0.092 mol) in CH2Cl2 (150 mL) was cooled at 0° C. Triethylamine (51.5 mL, 0.369 mol) was added slowly. CbzCl (13.59 mL, 0.092 mol) was added dropwise, keeping the temperature below 20° C. The reaction was allowed to warm overnight to room temperature. The reaction was quenched by addition of water and diluted further with additional CH2Cl2. The layers were separated and the organics were dried over MgSO4 and concentrated. The crude material was purified by silica gel gradient chromatography (0-75% ethyl acetate in hexanes), providing the titled compound as an oil.

Workup

  1. customthe temperature below 20° C
  2. temperatureto warm overnight to room temperature
  3. customThe reaction was quenched by addition of water
  4. additiondiluted further with additional CH2Cl2
  5. customThe layers were separated
  6. dry with materialthe organics were dried over MgSO4
  7. concentrationconcentrated
  8. customThe crude material was purified by silica gel gradient chromatography (0-75% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-3fdb670b55d3468ea2467a95aa697c3d
Source dataset
uspto-grants-2015_10
Patent number
US09156819B2

Reaction notes

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