p-Toluenesulfonic acid monohydrate → Tert-butyl 2-(acetoxymethyl)-4-hydroxypiperidine-1-carboxylate

HRID 2179412Notes

Reaction equation

HRID 2179412 reaction equation
[C:1]([O:4][CH2:5][CH:6]1[CH2:11][CH:10]([O:12]C2CCCCO2)[CH2:9][CH2:8][N:7]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])(=[O:3])[CH3:2].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[C:1]([O:4][CH2:5][CH:6]1[CH2:11][CH:10]([OH:12])[CH2:9][CH2:8][N:7]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])(=[O:3])[CH3:2]

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 68109037tert-butyl 2-(acetoxymethyl)-4-((tetrahydro-2H-pyran-2-yl)oxy)piperidine-1-carboxylate

Product 1

HCID 68109163Tert-butyl 2-(acetoxymethyl)-4-hydroxypiperidine-1-carboxylateYield 83%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of the product of step G (710 mg, 2.3 mmol) in methanol (20 mL) was added p-toluenesulfonic acid monohydrate (20 mg, 0.1 mmol). After stirring at ambient temperature for 4 h the solution was concentrated in vacuo to afford the crude product. Purification by flash column chromatography (SiO2, 19:1 to 7:3, hexanes/ethyl acetate) afforded tert-butyl 2-(acetoxymethyl)-4-hydroxypiperidine-1-carboxylate (506 mg, 83%) as a colorless oil: 1H NMR (CDCl3, 300 MHz) δ 4.49-4.41 (m, 2H), 4.33-4.05 (m, 3H), 3.94-3.88 (m, 1H), 3.29-3.21 (s, 1H), 2.05 (s, 3H), 1.89-1.80 (m, 1H), 1.76-1.69 (m, 2H), 1.46 (s, 9H).

Workup

  1. concentrationwas concentrated in vacuo
  2. customto afford the crude product
  3. customPurification by flash column chromatography (SiO2, 19:1 to 7:3, hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-142089934c1a47e7935d532ddc0710a9
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

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