Hydrochloric Acid → HCID 68502575, compound

HRID 2241038Notes

Reaction equation

HRID 2241038 reaction equation
[CH3:1][C:2]1([CH3:11])[CH2:7][C:6]([CH3:9])([CH3:8])[CH2:5][C:4](=O)[CH2:3]1.[C:12]1([C:18]([C:20]2[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][CH:21]=2)=O)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C1COCC1.Cl>C1(C)C=CC=CC=1.[Zn].Cl[Ti](Cl)(Cl)Cl.CCOC(C)=O.O>[C:12]1([C:18](=[C:4]2[CH2:3][C:2]([CH3:11])([CH3:1])[CH2:7][C:6]([CH3:9])([CH3:8])[CH2:5]2)[C:20]2[CH:21]=[CH:22][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:28][CH:29]=2)[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 843993,3,5,5-TetramethylcyclohexanoneHCID 349620Methyl 4-benzoylbenzoate

Product 1

HCID 68502575HCID 68502575, compoundYield 62.7%

Reagents, catalysts & solvents 5

HCID 23994ZincCatalystHCID 24193Titanium TetrachlorideCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

A stirred suspension of Zn dust (2.45 g, 37.5 mmol), 3,3,5,5-tetramethylcyclohexanone (1.93 g, 12.5 mmol), 19 (3.00 g, 12.5 mmol) and THF (100 mL) under N2 was cooled to −10° C. and a 1 M solution of TiCl4 in toluene (19.5 mL) was added, dropwise, over 10 min. After addition was complete the reaction was allowed to warm to room temperature and then heated at 90° C. for 7 h. The reaction was cooled to room temp and then chilled to −10° C. and concentrated HCl (15 mL) added dropwise followed by water (15 mL). The dark reaction turns a pale purple. EtOAc (60 mL) was added and the mixture washed with water (2×60 mL) and brine (1×60 mL) then dried (MgSO4) and concentrated to 5.1 g of a pale yellow oil. The crude product was purified by column chromatography on 200 g silica gel with a 100% hexanes to 2% EtOAc/hexanes gradient to afford 2.84 g of a white solid which was recrystallized from hexanes. Yield: 0.95 g (21%) of the title compound 20 which was contaminated with ˜5% of the pinacol intermediate. 1H NMR (400 MHz, DMSO-d6): δ 7.87 (d, J=8.2 Hz, 2H), 7.15-7.31 (m, 7H), 3.80 (s, 3H), 1.89 (s, 2H), 1.86 (s, 2H), 1.25 (s, 2H), 0.87 (s, 6H), 0.86 (s, 6H). Anal. Calcd for C25H30O2: C, 82.80; H, 8.36. Found: C, 82.94; H, 8.51.

Workup

  1. additionAfter addition
  2. temperatureto warm to room temperature
  3. temperatureheated at 90° C. for 7 h
  4. temperatureThe reaction was cooled to room temp
  5. temperaturechilled to −10° C.
  6. customThe dark reaction
  7. washthe mixture washed with water (2×60 mL) and brine (1×60 mL)
  8. dry with materialthen dried (MgSO4)
  9. concentrationconcentrated to 5.1 g of a pale yellow oil
  10. customThe crude product was purified by column chromatography on 200 g silica gel with a 100% hexanes to 2% EtOAc/hexanes gradient

Sources & evidence

ORD record
ord-9a63188b9a5042dcb95c68cfbfe9b03e
Source dataset
uspto-grants-2010_05
Patent number
US07723393B2

Reaction notes

Loading…