3-Butyn-1-OL → 4-[[4-(4-Hydroxy-1-butyn-1-yl)phenyl](3,3,5,5-tetramethylcyclohexylidene)methyl]phenol

HRID 229300Notes

Reaction equation

HRID 229300 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:39])[CH2:36][C:37]#[CH:38].[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:39][CH2:35][CH2:36][C:37]#[C:38][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]([CH3:24])([CH3:25])[CH2:17]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 135663-Butyn-1-OLHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 686545464-[(4-Iodophenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenol

Product 1

HCID 577572314-[[4-(4-Hydroxy-1-butyn-1-yl)phenyl](3,3,5,5-tetramethylcyclohexylidene)methyl]phenolYield 76.1%

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) (0.20 g, 0.45 mmol) in DMF (5 mL) were added Pd(PPh3)2Cl2 (32 mg, 0.05 mmol), CuI (9 mg, 0.05 mmol), N,N-diisopropylethylamine (0.36 mL, 2.02 mmol) and 3-butyn-1-ol (70 μL, 0.90 mmol). The reaction mixture was stirred at room temperature ovemight, poured into saturated aqueous NH4Cl (15 mL) and water (5 mL), extracted with ethyl acetate (2×50 mL). The combined organic phase was 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 40% EtOAc in hexanes to give a light brown solid. The solid was triturated with hot hexanes containing 2% MeOH and 2% CH2Cl2 to afford 133 mg (76%) of the title compound (242) as light beige solid. mp 183-184° C. 1H NMR (400 MHz, CH3OH-d6): δ 0.91 (s, 6H), 0.92 (s, 6H), 1.29 (s, 2H), 1.94 (s, 2H), 1.98 (s, 2H), 2.58 (t, J=6.8 Hz, 2H), 3.70 (t, J=6.8 Hz, 2H), 6.68 (d, J=8.6 Hz, 2H), 6.94 (d, J=8.4 Hz, 2H), 7.07 (d, J=8.3 Hz, 2H), 7.28 (d, J=8.0 Hz, 2H). LCMS (APCI): m/z 389 (M+H)+, 387 (M−H)−.

Workup

  1. extractionextracted with ethyl acetate (2×50 mL)
  2. washThe combined organic phase was 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 40% EtOAc in hexanes
  9. customto give a light brown solid
  10. customThe solid was triturated with hot hexanes containing 2% MeOH and 2% CH2Cl2

Sources & evidence

ORD record
ord-61132fea51eb4234a39a5f01c0bbdd66
Source dataset
uspto-grants-2009_07
Patent number
US07560589B2

Reaction notes

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