Propofol → (+/-)-[2,6-Bis(1-methylethyl)phenyl]nonyl Phosphoryl Chloride

HRID 247832

Reaction equation

HRID 247832 reaction equation
[P:1]([Cl:5])(Cl)([Cl:3])=[O:2].C(N(CC)CC)C.[CH:13]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH:22]([CH3:24])[CH3:23])[C:17]=1O)([CH3:15])[CH3:14].[CH2:26](O)[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]>C1(C)C=CC=CC=1.CCOC(C)=O.CCCCCC>[CH3:14][CH:13]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH:22]([CH3:24])[CH3:23])[C:17]=1[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][P:1]([Cl:5])([Cl:3])=[O:2])[CH3:15]

Participants

7

Reactant 4

HCID 4943PropofolHCID 8471TriethylamineHCID 89141-NonanolHCID 24813Phosphorus oxychloride

Product 1

HCID 131717894(+/-)-[2,6-Bis(1-methylethyl)phenyl]nonyl Phosphoryl ChlorideYield 91.3%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent3×HCID 21226206Ethyl acetate hexaneSolvent

Procedure

To a solution of phosphorus oxychloride (1.53 g, 10.0 mmol) and triethylamine (3.5 mL, 25.0 mmol) in toluene (20 mL) at 0° C. is added dropwise a solution of 2,6 diisopropylphenol (1.78 g, 10.0 mmol) in toluene (5 mL). The mixture is allowed to warm slowly to room temperature and stirred for 2 hours. The mixture is cooled to 0° C., and a solution of 1-nonanol (1.44 g, 10.0 mmol) in toluene (5 mL) is added dropwise. The mixture is allowed to warm to room temperature and stirred for 2 hours. The mixture is filtered and the filtrate concentrated to afford 4.1 g of a crude oil, which is taken up in 1:1 EtOAc/hexane and filtered through a small pad of silica gel. The filtrate is concentrated to afford 3.7 g of a light yellow liquid; 1H NMR (200 MHz, CDCl3)δ7.17 (br s, 3 H), 4.30-4.10 (m, 2 H), 3.43 (m, 2 H), 1.85-1.65 (m, 4 H), 1.45-1.10 (m, 10 H), 1.25 (d, J=7 Hz, 12 H), 0.89 (t, J=7 Hz, 3 H).

Workup

  1. temperatureThe mixture is cooled to 0° C.
  2. temperatureto warm to room temperature
  3. stirringstirred for 2 hours
  4. filtrationThe mixture is filtered
  5. concentrationthe filtrate concentrated
  6. customto afford 4.1 g of a crude oil, which
  7. filtrationfiltered through a small pad of silica gel
  8. concentrationThe filtrate is concentrated

Sources & evidence

ORD record
ord-b32f9da596774c468e388b6bebefa506
Source dataset
uspto-grants-1993_05
Patent number
US05208224

Linked notes

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