Water → HCID 21961318, compound

HRID 272361Notes

Reaction equation

HRID 272361 reaction equation
Br[C:2]1[C:3]([CH3:20])=[C:4]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[C:5]([CH3:11])=[C:6]([CH3:10])[C:7]=1[O:8][CH3:9].C([Li])CCC.[CH3:26][CH:27]([CH3:37])[C:28]([C:30]1[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=1)=[O:29].O>O1CCCC1>[OH:29][C:28]([C:2]1[C:3]([CH3:20])=[C:4]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[C:5]([CH3:11])=[C:6]([CH3:10])[C:7]=1[O:8][CH3:9])([C:30]1[CH:31]=[CH:32][C:33]([CH3:36])=[CH:34][CH:35]=1)[CH:27]([CH3:37])[CH3:26]

Participants

6

Reactant 4

HCID 962WaterHCID 5768291-Propanone, 2-methyl-1-(4-methylphenyl)-HCID 21961344HCID 21961344, compoundHCID 178418339Butyllithium

Product 1

HCID 21961318HCID 21961318, compoundYield 75.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 3-bromo-4-methoxy-2,5,6-trimethylphenylcarbamate (27.8 g, 80.8 mmol) in tetrahydrofuran (150 ml) was added at −78° C. n-butyllithium (1.6 M, 110 ml, 176 mmol) and the reaction mixture was stirred at the same temperature for 20 minutes. To the reaction solution was added 2-methyl-1-(4-methylphenyl)propan-1-one (13.1 g, 80.7 mmol) and stirred at room temperature for 1 hour. Water (150 ml) was added to the reaction mixture and the product was extracted three times with ethyl acetate. The combined organic layers were washed with water, dried on magnesium sulfate, filtered, and then concentrated under reduced pressure to obtain 26.0 g of tert-butyl 3-[1-hydroxy-2-methyl-1-(4-methylphenyl)propyl]-4-methoxy-2,5,6-trimethylphenylcarbamate as a crude product. A mixture of this compound and 47% hydrobromic acid (100 ml) was refluxed with heating for 4 hours under argon atmosphere. The reaction mixture was cooled down to room temperature and neutralized with an 8 N aqueous solution of sodium hydroxide. The product was extracted twice with ethyl acetate. The combined extracts were washed with an aqueous, saturated solution of sodium hydrogen carbonate, dried on magnesium sulfate, and then concentrated under reduced pressure. The residue was crystallized from isopropyl ether-hexane to obtain 14.8 g (62% yield) of the title compound. Melting point: 114-115° C.

Workup

  1. stirringstirred at room temperature for 1 hour
  2. extractionthe product was extracted three times with ethyl acetate
  3. washThe combined organic layers were washed with water
  4. customdried on magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a87ffb0c8df94666acfb2428fd3a307e
Source dataset
uspto-grants-2008_11
Patent number
US07456162B2

Reaction notes

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