Hydrochloric Acid → HCID 68501670, compound

HRID 2241034Notes

Reaction equation

HRID 2241034 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.[Br:12][C:13]1[CH:26]=[CH:25][C:16]([C:17]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=O)=[CH:15][CH:14]=1.C1COCC1.Cl>C1(C)C=CC=CC=1.[Zn].Cl[Ti](Cl)(Cl)Cl.CCOC(C)=O.O>[Br:12][C:13]1[CH:14]=[CH:15][C:16]([C:17]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[C:4]2[CH2:3][C:2]([CH3:11])([CH3:1])[CH2:7][C:6]([CH3:9])([CH3:8])[CH2:5]2)=[CH:25][CH:26]=1

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 70304-BromobenzophenoneHCID 8028TetrahydrofuranHCID 843993,3,5,5-Tetramethylcyclohexanone

Product 1

HCID 68501670HCID 68501670, compoundYield 58%

Reagents, catalysts & solvents 5

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

Conditions

Temperature
-10 °C

Procedure

A stirred suspension of Zn dust (3.76 g, 57.5 mmol), 3,3,5,5-tetramethyl cyclohexanone (2.95 g, 19.2 mmol), 4-bromobenzophenone (5.00 g, 19.15 mmol) and anhydrous THF (100 mL) under N2 was cooled to −10° C. and a 1 M solution of TiCl4 in toluene (30 mL) added, dropwise, over 10 min. The temperature was maintained below 0° C. during the addition. After addition was complete the reaction was allowed to warm to RT and then heated at 90° C. for 2 h. The reaction was cooled to −10° C. and concentrated HCl (15 mL) added dropwise followed by water (15 mL). After stirring 30 min, EtOAc (100 mL) was added and the pale yellow 2-phase mixture washed with water (2×75 mL) and brine (1×75 mL) then dried (MgSO4) and concentrated to 8.26 g of a pale yellow oil. The crude oil is purified by column chromatography on 250 g silica gel with 2% EtOAc/hexanes to afford 4.17 g (58%) of the title compound (16) as a white solid. 1H-NMR indicated that the product (16) was contaminated with ˜8% of an impurity consistent with the pinacol intermediate formed during the McMurry reaction. 1H NMR (400 MHz, DMSO-d6): δ7.46 (d, J=8.3 Hz, 2H), 7.28 (t, J=7.5 Hz, 2H), 7.04-7.19 (m, 5H), 1.87 (s, 4H), 1.24 (s, 2H), 0.87 (s, 6H), 0.86 (s, 6H).

Workup

  1. temperatureThe temperature was maintained below 0° C. during the addition
  2. additionAfter addition
  3. temperatureto warm to RT
  4. temperatureheated at 90° C. for 2 h
  5. temperatureThe reaction was cooled to −10° C.
  6. washthe pale yellow 2-phase mixture washed with water (2×75 mL) and brine (1×75 mL)
  7. dry with materialthen dried (MgSO4)
  8. concentrationconcentrated to 8.26 g of a pale yellow oil
  9. customThe crude oil is purified by column chromatography on 250 g silica gel with 2% EtOAc/hexanes

Sources & evidence

ORD record
ord-69e26244e0d84e849a2fbd46f373488a
Source dataset
uspto-grants-2010_05
Patent number
US07723393B2

Reaction notes

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