Hydrochloric Acid → 4-[[2'-(Hydroxymethyl)-4-biphenylyl](3,3,5,5-tetramethylcyclohexylidene)methyl]phenol

HRID 2100210Notes

Reaction equation

HRID 2100210 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[C:25]2[CH2:30][C:29]([CH3:32])([CH3:31])[CH2:28][C:27]([CH3:34])([CH3:33])[CH2:26]2)[C:9]2[CH:14]=[CH:13][C:12]([C:15]3[C:16]([C:21](OC)=[O:22])=[CH:17][CH:18]=[CH:19][CH:20]=3)=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].CCOC(C)=O.Cl>C1COCC1>[OH:22][CH2:21][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[C:12]1[CH:13]=[CH:14][C:9]([C:8](=[C:25]2[CH2:26][C:27]([CH3:34])([CH3:33])[CH2:28][C:29]([CH3:32])([CH3:31])[CH2:30]2)[C:5]2[CH:4]=[CH:3][C:2]([OH:1])=[CH:7][CH:6]=2)=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 21226445Aluminium lithium hydrideHCID 68654495Methyl 4'-[(4-hydroxyphenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]-2-biphenylcarboxylate

Product 1

HCID 577572234-[[2'-(Hydroxymethyl)-4-biphenylyl](3,3,5,5-tetramethylcyclohexylidene)methyl]phenolYield 87%

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]-2-biphenylcarboxylate (248) (0.102 g, 0.23 mmol) in THF (8 mL) at 0° C. was added lithium aluminum hydride (1 M in THF, 0.56 mL, 0.56 mmol) dropwise. The reaction mixture was stirred at 0° C. for 1 h. EtOAc (5 mL) was added, and stirring continued for 10 minutes. 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 washed with water, brine and dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as light yellow oil. The crude product was purified by flash chromatography over SiO2 eluted with a gradient from hexanes to 40% EtOAc in hexanes to give 83 mg (87%) of the title compound (250) as a white solid. mp 171-172° C. 1H NMR (400 MHz, DMSO-d6): δ 0.88 (s, 6H), 0.90 (s, 6H), 1.25(s, 2H), 1.91 (s, 2H), 1.92 (s, 2H), 4.36 (d, J=5.1 Hz, 2H), 5.10 (t, J=5.3 Hz, 1H), 6.67 (d, J=8.2 Hz, 2H), 6.96 (d, J=8.2 Hz, 2H), 7.12-7.23 (m, 3H), 7.24-7.36 (m, 4H), 7.53 (d, J=7.5 Hz, 1H), 9.27 (s, 1H). LCMS (ESI): m/z 425 (M−H)−.

Workup

  1. stirringstirring
  2. waitcontinued for 10 minutes
  3. extractionextracted with EtOAc (2×50 mL)
  4. extractionThe combined organic extract
  5. washwashed with water, brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated
  9. customto give the crude product as light yellow oil
  10. customThe crude product was purified by flash chromatography over SiO2
  11. washeluted with a gradient from hexanes to 40% EtOAc in hexanes

Sources & evidence

ORD record
ord-95aa194550a242e19d07914f1e19a3df
Source dataset
uspto-grants-2009_08
Patent number
US07569601B2

Reaction notes

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