Hydrogen Bromide → HCID 18672235, compound

HRID 488831Notes

Reaction equation

HRID 488831 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7]O)=[CH:5][C:4]=1[C:11]1[C:20]([CH3:21])=[CH:19][C:18]2[C:17]([CH3:23])([CH3:22])[CH2:16][CH:15]([CH3:24])[CH:14]([CH3:25])[C:13]=2[CH:12]=1.[BrH:26]>C(O)(=O)C.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][Br:26])=[CH:5][C:4]=1[C:11]1[C:20]([CH3:21])=[CH:19][C:18]2[C:17]([CH3:23])([CH3:22])[CH2:16][CH:15]([CH3:24])[CH:14]([CH3:25])[C:13]=2[CH:12]=1

Participants

5

Reactant 2

HCID 260Hydrogen BromideHCID 69461754HCID 69461754, compound

Product 1

HCID 18672235HCID 18672235, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-methoxy-3-(3,5,5,8,7-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl) benzyl alcohol (195 mg, 0.57 mmol) in acetic acid (glacial, 3 mL) was added HBr (48%, 1 mL) and the resulting mixture heated at reflux for 2 hours. The solution was cooled to room temperature, diluted with ethyl acetate and washed successively with water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated to afford 200 mg of crude 4-methoxy-3-(3,5,5,8,7-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl) benzyl bromide. To a stirred solution of 2,4-thiazolidinedione (133 mg, 1.14 mmol) in anhydrous THF (6 mL) was added, at −78° C. under argon, n-BuLi (1.6M in hexane, 1.5 mL, 2.4 mmol) dropwise. The mixture was maintained at −78° C. for 15 minutes and then warmed to 0° C. for 30 minutes to complete the dianion formation. Upon recooling to −78° C., 4-methoxy-3-(3,5,5,8,7-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl) benzyl bromide was added in THF (3 mL). After 30 minutes the orange solution was allowed to warm to room temperature. After 1.5 hours, the solution was treated with 2N HCl, diluted with ethyl acetate and washed successively with water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was chromatographed on silica gel (eluent:ethyl acetate/hexane 2:8) to give 61 mg of 5-[4-methoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)benzyl] thiazolidine-2,4-dione (24% for 3 steps from benzaldehyde). 1H NMR (500 MHz; CDCl3): δ 1.27 (s, 6 H); 1.26 (s, 6 H); 1.69 (s, 4 H); 2.08 (s, 3 H); 3.12 (dd, J1=14.0 Hz, J2=9.5 Hz, 1 H); 3.50 (dd, J1=14.0 Hz, J2=4.0 Hz, 1 H); 3.76(s, 3 H); 4.54 (dd, J1=9.5 Hz, J2=4.0 Hz, 1 H); 6.89 (d, J=8.0 Hz, 1 H); 7.03 (d, J=2 Hz, 1 H); 7.07 (s, 1 H); 7.14 (s, 1 H); 7.17 (dd, J1=8.0 Hz, J2=2.0 Hz, 1 H), 7.95 (br, 1 H).

Workup

  1. temperaturethe resulting mixture heated
  2. temperatureat reflux for 2 hours
  3. washwashed successively with water and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-95aa1a13f2414d2193da40c85c583fff
Source dataset
uspto-grants-2005_12
Patent number
US06974826B2

Reaction notes

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