Hydrochloric Acid → 3-(3-{Hydroxy-[3-(3-hydroxy-2,2-dimethylpropyl)-phenyl]-methyl}-phenyl)-2,2-dimethylpropan-1-ol

HRID 1466722Notes

Reaction equation

HRID 1466722 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].C([O:9][C:10](=O)[C:11]([CH3:37])([CH3:36])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19](=[O:35])[C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][C:27]([C:30](OCC)=[O:31])([CH3:29])[CH3:28])[CH:21]=2)[CH:14]=1)C.C(OCC)(=O)C.Cl>CC(OC)(C)C>[OH:35][CH:19]([C:15]1[CH:16]=[CH:17][CH:18]=[C:13]([CH2:12][C:11]([CH3:37])([CH3:36])[CH2:10][OH:9])[CH:14]=1)[C:20]1[CH:21]=[C:22]([CH2:26][C:27]([CH3:29])([CH3:28])[CH2:30][OH:31])[CH:23]=[CH:24][CH:25]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 112591923-{3-[3-(2-Ethoxycarbonyl-2-methylpropyl)-benzoyl]phenyl}-2,2-dimethylpropionic acid ethyl esterHCID 21226445Aluminium lithium hydride

Product 1

HCID 666171083-(3-{Hydroxy-[3-(3-hydroxy-2,2-dimethylpropyl)-phenyl]-methyl}-phenyl)-2,2-dimethylpropan-1-olYield 90.3%

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent2×

Procedure

Under Ar atmosphere, to a suspension of LiAlH4 (7.90 g, 208 mmol) in MTBE (200 mL) was added dropwise a solution of 3-{3-[3-(2-ethoxycarbonyl-2-methylpropyl)-benzoyl]phenyl}-2,2-dimethylpropionic acid ethyl ester (25.9 g, 59 mmol) in MTBE (150 mL). The reaction mixture was stirred at room temperature for 16 h and heated to reflux for 3 h. Ethyl acetate (100 mL) was added and the reaction mixture was heated to reflux for 1 h and cooled to room temperature. The reaction mixture was poured into ice (500 g) and acidified with hydrochloric acid solution (2 N, 800 mL). The aqueous solution was extracted with MTBE (4×200 mL). The combined organic layers were washed with saturated NaHCO3 solution (200 mL) and saturated NaCl solution (200 mL), dried over MgSO4, and concentrated under vacuum. The residue (22.6 g) was subjected to column chromatography on silica gel using hexanes/ethyl acetate (3:2) as eluent to afford 3-(3-{hydroxy-[3-(3-hydroxy-2,2-dimethylpropyl)-phenyl]-methyl}-phenyl)-2,2-dimethylpropan-1-ol (19.0 g, 90%) as a white solid. Mp 98-99° C. 1H NMR (300 MHz, CDCl3/TMS): δ (ppm): 7.26-7.19 (m, 6H), 7.06-7.03 (m, 2H), 5.80 (d, 1H, J=3.4 Hz), 3.23 (s, 4H), 3.05 (d, 1H, J=3.4 Hz), 2.56 (s, 4H), 2.07 (br d, 2H, J=4.4 Hz), 0.85 (s, 12H). 13C NMR (75 MHz, CD3OD=49.15 ppm): δ (ppm): 145.5, 140.2, 130.5, 130.1, 128.7, 125.4, 77.1, 71.5, 45.6, 37.4, 24.6, 24.5. HRMS (FAB, gly): Calcd for C23H33O3 (M+H): 357.2430. found: 357.2388. HPLC: 99.8% pure.

Workup

  1. temperatureheated
  2. temperatureto reflux for 3 h
  3. temperaturethe reaction mixture was heated
  4. temperatureto reflux for 1 h
  5. temperaturecooled to room temperature
  6. extractionThe aqueous solution was extracted with MTBE (4×200 mL)
  7. washThe combined organic layers were washed with saturated NaHCO3 solution (200 mL) and saturated NaCl solution (200 mL)
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-c98492c40f6d4e5690abe870bdb8df6f
Source dataset
uspto-grants-2015_04
Patent number
US09000041B2

Reaction notes

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