1,2,4-Butanetriol → LNP Lipid-7

HRID 2280989Notes

Reaction equation

HRID 2280989 reaction equation
[CH2:1]([C:19]([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]/[CH:29]=[CH:30]\[CH2:31]/[CH:32]=[CH:33]\[CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])=[O:20])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11]/[CH:12]=[CH:13]\[CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[CH2:39]([OH:45])[CH2:40][CH:41]([OH:44])[CH2:42]O.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>C1(C)C=CC=CC=1>[CH2:1]([C:19]1([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]/[CH:29]=[CH:30]\[CH2:31]/[CH:32]=[CH:33]\[CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])[O:44][CH:41]([CH2:40][CH2:39][OH:45])[CH2:42][O:20]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11]/[CH:12]=[CH:13]\[CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]

Participants

5

Reactant 3

HCID 183021,2,4-ButanetriolHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 59544992Bis(linoleyl) ketone

Product 1

HCID 58275668LNP Lipid-7

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of dilinoleyl ketone (I, previously prepared as described in Example 1, 527 mg, 1.0 mmol), 1,3,4-butanetriol (technical grade, ca. 90%, 236 mg, 2 mmol) and pyridinium p-toluenesulfonate (50 mg, 0.2 mmol) in 50 mL of toluene was refluxed under nitrogen overnight with a Dean-Stark tube to remove water. The resulting mixture was cooled to room temperature. The organic phase was washed with water (2×30 mL), brine (50 mL), and dried over anhydrous Na2SO4. Evaporation of the solvent resulted in a yellowish oily residual (0.6 g). The crude product was purified by column chromatography on silica gel (230-400 mesh, 100 mL) with dichloromethane as eluent. This afforded 0.5 g of pure II as colourless oil. 1H NMR (400 MHz, CDCl3) δ: 5.25-5.48 (8H, m, 4×CH═CH), 4.18-4.22 (1H, m, OCH), 4.08 (1H, dd, OCH), 3.82 (2H, t, OCH2), 3.53 (1H, t, OCH), 2.78 (4H, t, 2×C═C—CH2—C═C), 2.06 (8H, q, 4×allylic CH2), 1.77-1.93 (2H, m, CH2), 1.52-1.68 (4H, m, 2×CH2), 1.22-1.45 (32H, m), 0.86-0.94 (6H, t, 2×CH3) ppm.

Workup

  1. custompreviously prepared
  2. temperaturewas refluxed under nitrogen overnight with a Dean-Stark tube
  3. customto remove water
  4. washThe organic phase was washed with water (2×30 mL), brine (50 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. customEvaporation of the solvent
  7. customresulted in a yellowish oily residual (0.6 g)
  8. customThe crude product was purified by column chromatography on silica gel (230-400 mesh, 100 mL) with dichloromethane as eluent

Sources & evidence

ORD record
ord-97434327f21e45ff85258c72a611b1d8
Source dataset
uspto-grants-2015_09
Patent number
US09139554B2

Reaction notes

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