Hydrochloric Acid → HCID 9803137, compound

HRID 1884499Notes

Reaction equation

HRID 1884499 reaction equation
[S:1]1[CH2:5][C:4](=[O:6])[NH:3][C:2]1=[O:7].[Li][CH2:9]CCC.[CH3:13][O:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19]Br)=[CH:17][C:16]=1[C:23]1[C:32]([CH3:33])=[CH:31][C:30]2[C:29]([CH3:35])([CH3:34])[CH2:28][CH:27](C)[CH:26]([CH3:37])[C:25]=2[CH:24]=1.Cl>C1COCC1.C(OCC)(=O)C>[CH3:13][O:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19][CH:5]2[S:1][C:2](=[O:7])[NH:3][C:4]2=[O:6])=[CH:17][C:16]=1[C:23]1[C:32]([CH3:33])=[CH:31][C:30]2[C:29]([CH3:35])([CH3:34])[CH2:28][CH2:27][C:26]([CH3:37])([CH3:9])[C:25]=2[CH:24]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 5437ThiazolidinedioneHCID 18672235HCID 18672235, compoundHCID 178418339Butyllithium

Product 1

HCID 9803137HCID 9803137, compoundYield 24%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

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): δ1.27 (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. temperaturewarmed to 0° C. for 30 minutes
  2. customUpon recooling to −78° C.
  3. temperatureto warm to room temperature
  4. waitAfter 1.5 hours
  5. washwashed successively with water and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was chromatographed on silica gel (eluent: ethyl acetate/hexane 2:8)

Sources & evidence

ORD record
ord-6f924bef302443c696dd736c11549848
Source dataset
uspto-grants-2004_07
Patent number
US06765013B2

Reaction notes

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