Hydrochloric Acid → 4-[[4-(2-Hydroxyethyl)phenyl](3,3,5,5-tetramethylcyclohexylidene)methyl]phenol

HRID 229291Notes

Reaction equation

HRID 229291 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[C:20]2[CH2:25][C:24]([CH3:27])([CH3:26])[CH2:23][C:22]([CH3:29])([CH3:28])[CH2:21]2)[C:9]2[CH:14]=[CH:13][C:12]([CH2:15][C:16](OC)=[O:17])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].CCOC(C)=O.Cl>C1COCC1>[OH:17][CH2:16][CH2:15][C:12]1[CH:13]=[CH:14][C:9]([C:8](=[C:20]2[CH2:21][C:22]([CH3:29])([CH3:28])[CH2:23][C:24]([CH3:27])([CH3:26])[CH2:25]2)[C:5]2[CH:6]=[CH:7][C:2]([OH:1])=[CH:3][CH:4]=2)=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 21226445Aluminium lithium hydrideHCID 86613510Methyl{4-[(4-hydroxyphenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenyl}acetate

Product 1

HCID 577572284-[[4-(2-Hydroxyethyl)phenyl](3,3,5,5-tetramethylcyclohexylidene)methyl]phenolYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of methyl {4-[(4-hydroxyphenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenyl}acetate (153) (0.22 g, 0.56 mmol) in THF (10 mL) at 0° C. was added LAH (1 M in THF, 1.40 mL, 1.40 mmol) dropwise. The reaction mixture was stirred at 0° C. for 1 h, EtOAc (5 mL) was added, and stirring continued for 10 min. The mixture was then acidified to pH=2 with an aqueous solution of 1 N HCl, extracted with EtOAc (2×50 mL). The combined organic extract was washed with water, brine and dried (Na2SO4) filtered, and the filtrate was concentrated to give the crude product as colorless oil. The crude product was purified by flash chromatography on silica gel eluted with a gradient from hexanes to 40% EtOAc:hexanes to give a white residue, which upon trituration with hot hexanes containing 1% of MeOH yielded 0.185 g (91%) of the title compound 232 as a white solid. mp 159-160° C. 1H NMR (400 MHz, DMSO-d6): δ 0.87 (s, 12H), 1.23 (s, 2H), 1.87 (s, 2H), 1.89 (s, 2H), 2.65 (t, J=7.1 Hz, 2H), 3.50-3.60 (m, 2H), 4.58 (t, J=5.2 Hz, 1H), 6.64 (d, J=8.2 Hz, 2H), 6.90 (d, J=8.4 Hz, 2H), 7.00 (d, J=7.9 Hz, 2H), 7.10 (d, J=8.1 Hz, 2H), 9.22 (s, 1H). LCMS (ES): m/z 365 (M+H)+, 363 (M−H)−.

Workup

  1. stirringstirring
  2. waitcontinued for 10 min
  3. extractionextracted with EtOAc (2×50 mL)
  4. extractionThe combined organic extract
  5. washwas washed with water, brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated
  9. customto give the crude product as colorless oil
  10. customThe crude product was purified by flash chromatography on silica gel
  11. washeluted with a gradient from hexanes to 40% EtOAc
  12. customhexanes to give a white residue, which upon trituration with hot hexanes containing 1% of MeOH

Sources & evidence

ORD record
ord-094cc610fda84c77aac773ba456c8e7b
Source dataset
uspto-grants-2009_07
Patent number
US07560589B2

Reaction notes

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