Propargyl alcohol → 4-[[4-(3-Hydroxy-1-propyn-1-yl)phenyl](3,3,5,5-tetramethylcyclohexylidene)methyl]phenol

HRID 2100127Notes

Reaction equation

HRID 2100127 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([C:8](=[C:16]2[CH2:21][C:20]([CH3:23])([CH3:22])[CH2:19][C:18]([CH3:25])([CH3:24])[CH2:17]2)[C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[CH2:35]([OH:38])[C:36]#[CH:37].[NH4+].[Cl-]>CN(C=O)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.O>[OH:38][CH2:35][C:36]#[C:37][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[C:16]2[CH2:17][C:18]([CH3:24])([CH3:25])[CH2:19][C:20]([CH3:22])([CH3:23])[CH2:21]2)[C:9]2[CH:10]=[CH:11][C:12]([OH:15])=[CH:13][CH:14]=2)=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 7859Propargyl alcoholHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 686545464-[(4-Iodophenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenol

Product 1

HCID 112341984-[[4-(3-Hydroxy-1-propyn-1-yl)phenyl](3,3,5,5-tetramethylcyclohexylidene)methyl]phenolYield 74.5%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a degassed solution of 4-[(4-iodophenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenol (144) (0.17 g, 0.38 mmol) in DMF (3 mL) were added Pd(PPh3)2Cl2 (27 mg, 0.04 mmol), CuI (8 mg, 0.04 mmol), N,N-diisopropylethylamine (0.30 mL, 1.71 mmol) and propargyl alcohol (45 μL, 0.76 mmol). The reaction mixture was stirred at room temperature overnight, poured into saturated aqueous NH4Cl (15 mL) and water (5 mL), extracted with EtOAc (3×50 mL). The combined organic phase washed with water, brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as brown oil. The crude product was purified by chromatography on a silica gel column eluted with a gradient from hexanes to 30% EtOAc:hexanes to give 0.106 g (74%) of compound 145 as pale yellow solid. mp 141-142° C. 1H NMR (400 MHz, DMSO-d6): δ 0.85 (s, 6H), 0.87 (s, 6H), 1.23 (s, 2H), 1.85 (s, 2H), 1.89 (s, 2H), 4.25 (d, J=5.9 Hz, 2H), 5.28 (t, J=5.9 Hz, 1H), 6.65 (d, J=8.4 Hz, 2H), 6.91 (d, J=8.2 Hz, 2H), 7.10 (d, J=8.0 Hz, 2H), 7.31 (d, J=8.0 Hz, 2H), 9.29 (s, 1H). LCMS (ESI): m/z 375 (M+H)+, 373 (M−H)−. Anal. Calcd for C26H30O2.0.1H2O: C, 82.98; H, 8.09; Found: C, 82.88; H, 8.19.

Workup

  1. extractionextracted with EtOAc (3×50 mL)
  2. washThe combined organic phase washed with water, brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated
  6. customto give the crude product as brown oil
  7. customThe crude product was purified by chromatography on a silica gel column
  8. washeluted with a gradient from hexanes to 30% EtOAc

Sources & evidence

ORD record
ord-ca70ee9b1fb6460bacef147fb0524732
Source dataset
uspto-grants-2009_08
Patent number
US07569601B2

Reaction notes

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