Potassium Carbonate → Tert-butyl 4-{[(3,4-dioxo-3,4-dihydronaphthalen-1-yl)thio]methyl}-4-hydroxypiperidine-1-carboxylate

HRID 1665274Notes

Reaction equation

HRID 1665274 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](=[O:12])[C:4](=[O:13])[CH:3]=1.[OH:14][C:15]1([CH2:28][SH:29])[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[O:13]=[C:4]1[C:5](=[O:12])[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2]([S:29][CH2:28][C:15]2([OH:14])[CH2:16][CH2:17][N:18]([C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22])[CH2:19][CH2:20]2)=[CH:3]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 5823914-Chloronaphthalene-1,2-dioneHCID 53438219Tert-butyl 4-hydroxy-4-(mercaptomethyl)piperidine-1-carboxylate

Product 1

HCID 57661963Tert-butyl 4-{[(3,4-dioxo-3,4-dihydronaphthalen-1-yl)thio]methyl}-4-hydroxypiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 4-chloronaphthalene-1,2-dione (1.0 g, 5.2 mmol) and tert-butyl 4-hydroxy-4-(mercaptomethyl)piperidine-1-carboxylate (1.348 g, 5.45 mmol) in acetonitrile (20 mL) was added potassium carbonate (2.16 g, 15.6 mmol). The reaction was stirred at room temperature for 2 hours. To the reaction mixture was then added EtOAc (40 mL) and the reaction mixture filtered through celite. The solvent was then removed under reduced pressure. The crude foamy residue was dissolved in EtOAc (40 mL) and the solvent once again removed under reduced pressure. To the crude foamy solid was added EtOAc (7 mL) and the reaction mixture stirred for 10 min. An orange solid separated out. Diethyl ether (20 mL) was then added and the solution was left in the refrigerator to ensure that most of the product crashed out. The solid was filtered and washed with diethyl ether to afford the product as an orange solid. The mother liquor was concentrated under reduced pressure and purified by flash column chromatography (SiO2, 40% EtOAc in hexanes) to recover the product (1.66 g, 80%) as an orange solid. M.p.=156-157° C.; 400 MHz 1H NMR (CDCl3) δ: 8.2-8.14 (m, 1H), 7.9-7.86 (m, 1H), 7.72-7.66 (m, 1H), 7.61-7.55 (m, 1H), 6.50 (s, 1H), 4.05-3.85 (m, 2H), 3.25-3.1 (m, 2H), 3.19 (s, 2H), 1.9-1.7 (m, 5H), 1.47 (s, 9H); LCMS: 404 [M+H].

Workup

  1. filtrationadded EtOAc (40 mL) and the reaction mixture filtered through celite
  2. customThe solvent was then removed under reduced pressure
  3. dissolutionThe crude foamy residue was dissolved in EtOAc (40 mL)
  4. customthe solvent once again removed under reduced pressure
  5. additionTo the crude foamy solid was added EtOAc (7 mL)
  6. stirringthe reaction mixture stirred for 10 min
  7. customAn orange solid separated out
  8. additionDiethyl ether (20 mL) was then added
  9. waitthe solution was left in the refrigerator
  10. filtrationThe solid was filtered
  11. washwashed with diethyl ether

Sources & evidence

ORD record
ord-58a1d7bf2d8c40e9911dcdaf74d3e2e7
Source dataset
uspto-grants-2011_10
Patent number
US08039503B2

Reaction notes

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