Triethylamine → 3-(3-(Hydroxymethyl)phenyl)prop-2-yn-1-ol

HRID 446386Notes

Reaction equation

HRID 446386 reaction equation
I[C:2]1[CH:3]=[C:4]([CH2:8][OH:9])[CH:5]=[CH:6][CH:7]=1.C([Si](C)(C)[O:15][CH2:16][C:17]#[CH:18])(C)(C)C.C(N(CC)CC)C>CN1C(=O)CCC1.O.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:9][CH2:8][C:4]1[CH:3]=[C:2]([C:18]#[C:17][CH2:16][OH:15])[CH:7]=[CH:6][CH:5]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 423003-Iodobenzyl alcoholHCID 3445622tert-Butyl(dimethyl)[(prop-2-yn-1-yl)oxy]silane

Product 1

HCID 581685523-(3-(Hydroxymethyl)phenyl)prop-2-yn-1-ol

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Copper (I) iodide (0.037 g) and tetrakis(triphenylphosphine)palladium (0) (0.075 g) were added to a solution of (3-iodophenyl)methanol (2.27 g), tert-butyldimethyl(prop-2-ynyloxy)silane (1.1 g) and triethylamine (2.7 mL) in NMP (20 mL) and the mixture stirred at ambient temperature under nitrogen for 18 hours. The mixture was diluted with water and extracted into ethyl acetate (×3). The combined extracts were washed successively with 10% brine, 30% brine and saturated brine, dried over magnesium sulfate, filtered and the solvent removed. The crude product was purified by flash silica chromatography, elution gradient 10, 15 and 20% ethyl acetate in isohexane. Appropriate fractions were evaporated to dryness to give a mixture of product and starting material. The mixture was purified by preparative HPLC (XBridge™, Gradient: 65-99% acetonitrile in 0.2% aqueous TFA) to afford the subtitled compound as a pale yellow oil. Yield 0.44 g.

Workup

  1. extractionextracted into ethyl acetate (×3)
  2. washThe combined extracts were washed successively with 10% brine, 30% brine and saturated brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. customthe solvent removed
  6. customThe crude product was purified by flash silica chromatography, elution gradient 10, 15 and 20% ethyl acetate in isohexane
  7. customAppropriate fractions were evaporated to dryness
  8. customto give
  9. additiona mixture of product
  10. customThe mixture was purified by preparative HPLC (XBridge™, Gradient: 65-99% acetonitrile in 0.2% aqueous TFA)

Sources & evidence

ORD record
ord-be58c6d69fa142d09f916a89061a1c16
Source dataset
uspto-grants-2013_07
Patent number
US08476265B2

Reaction notes

Loading…