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

HRID 1665267Notes

Reaction equation

HRID 1665267 reaction equation
[C:1]1(=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]1=[O:11].[OH:13][C:14]1([CH2:27][SH:28])[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1.C(N(CC)CC)C>C(#N)C>[O:11]=[C:2]1[C:1](=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([S:28][CH2:27][C:14]2([OH:13])[CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])[CH2:18][CH2:19]2)=[CH:3]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 106671,2-NaphthoquinoneHCID 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-carboxylateYield 294.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of naphthalene-1,2-dione (3.2 g, 2.02 mmol) and tert-butyl 4-hydroxy-4-(mercaptomethyl)piperidine-1-carboxylate (5.0 g, 2.02 mmol) in anhydrous acetonitrile (400 ml) was added triethylamine (2.82 ml, 2.02 mmol). The reaction mixture was allowed to stir for 1 hour at room temperature and the solvents were evaporated under reduced pressure. The crude product was purified by flash column chromatography (SiO2, 40% EtOAc in hexanes to 70% EtOAc in hexanes). Fractions containing the product were concentrated and tritrated with ethyl acetate/ether to afford the desired product as a red solid (2.4 g, 29%). M.p.=156-157° C.; 400 MHz 1H NMR (CDCl3) δ: 8.17-8.12 (m, 1H), 7.87-7.83 (m, 1H), 7.69-7.62 (m, 1H), 7.59-7.52 (m, 1H), 6.49 (s, 1H), 4.0-3.85 (m, 2H), 3.25-3.14 (m, 4H), 1.84-1.78 (m, 2H), 1.76-1.66 (m, 2H), 1.47 (s, 9H); LCMS: 404 [M+H].

Workup

  1. customthe solvents were evaporated under reduced pressure
  2. customThe crude product was purified by flash column chromatography (SiO2, 40% EtOAc in hexanes to 70% EtOAc in hexanes)
  3. additionFractions containing the product
  4. concentrationwere concentrated

Sources & evidence

ORD record
ord-8e13a36479ff4b0a9b68ac58ec7fa30c
Source dataset
uspto-grants-2011_10
Patent number
US08039503B2

Reaction notes

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