Propargyl alcohol → Ethyl 2-[3-(3-hydroxy-propyl)-phenoxy]-2-methyl-propionate

HRID 2234863Notes

Reaction equation

HRID 2234863 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=1)[O:5][C:6]([CH3:13])([CH3:12])[C:7]([O:9][CH2:10][CH3:11])=[O:8].[CH2:17]([OH:20])[C:18]#[CH:19]>C(NC(C)C)(C)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[OH:20][CH2:17][CH2:18][CH2:19][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=1)[O:5][C:6]([CH3:13])([CH3:12])[C:7]([O:9][CH2:10][CH3:11])=[O:8]

Participants

6

Reactant 2

HCID 7859Propargyl alcoholHCID 5197437Ethyl 2-(3-bromophenoxy)-2-methylpropanoate

Product 1

HCID 59298819Ethyl 2-[3-(3-hydroxy-propyl)-phenoxy]-2-methyl-propionate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 7912DiisopropylamineSolvent

Procedure

10d (50 g, 175 mmol) is placed in the presence of 2-propynol (12 ml, 210 mmol) in 400 ml of diisopropylamine, under nitrogen. Pd(PPh3)2Cl2 (3.5 g) and CuI (500 mg) are added and the reaction medium is stirred at reflux for 5 h. The precipitate formed in the course of the reaction is filtered on celite and the reaction medium is dry concentrated. The oil obtained is purified by flash chromatography on silica (petroleum ether:AcOEt 80:20). It is then placed in a solution of 250 ml of THF and 150 ml of EtOH in the presence of Pd/C under hydrogen at 6 bar. This mixture is stirred for 24 h. at ambient temperature. After filtration on celite, the reaction medium is dry concentrated and 12a is isolated in the form of a clear oil (32 g, yield=69%). TLC silica gel 60 F 254 Merck, heptane:AcOEt 80:20, Rf=0.56.

Workup

  1. temperatureat reflux for 5 h
  2. customThe precipitate formed in the course of the reaction
  3. filtrationis filtered on celite
  4. customthe reaction medium is dry
  5. concentrationconcentrated
  6. customThe oil obtained
  7. customis purified by flash chromatography on silica (petroleum ether:AcOEt 80:20)
  8. stirringThis mixture is stirred for 24 h. at ambient temperature
  9. filtrationAfter filtration on celite
  10. customthe reaction medium is dry
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-826867f87522456b842a20cec60cfc5b
Source dataset
uspto-grants-2010_05
Patent number
US07713971B2

Reaction notes

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