Methanol → ethyl (1-hydroxy-6-methyl-2,3-dihydro-1H-inden-2-yl)carbamate

HRID 1893513Notes

Reaction equation

HRID 1893513 reaction equation
[Si](O[N:9]=[C:10]1[CH2:18][C:17]2[C:12](=[CH:13][C:14]([CH3:19])=[CH:15][CH:16]=2)[C:11]1=[O:20])(C(C)(C)C)(C)C.CO.C(N(CC)CC)C.Cl[C:31]([O:33][CH2:34][CH3:35])=[O:32]>O1CCCC1.ClCCl.O>[OH:20][CH:11]1[C:12]2[C:17](=[CH:16][CH:15]=[C:14]([CH3:19])[CH:13]=2)[CH2:18][CH:10]1[NH:9][C:31](=[O:32])[O:33][CH2:34][CH3:35]

Participants

8

Reactant 4

HCID 887MethanolHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 866507766-methyl-1H-inden-1,2(3H)-dione 2-{O-[tert-butyl(dimethyl)silyl]oxime}

Product 1

HCID 86650777ethyl (1-hydroxy-6-methyl-2,3-dihydro-1H-inden-2-yl)carbamateYield 67.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
63 °C

Procedure

The compound (6.00 g, 20.7 mmol) obtained in step B was dissolved in tetrahydrofuran (100 ml), and the mixture was stirred with heating at 63° C. At the same temperature, 1 mol/L borane-tetrahydrofuran complex/tetrahydrofuran solution (41.4 ml, 41.4 mmol) was slowly added dropwise. The mixture was stirred at the same temperature for 2.5 hr, cooled to room temperature and methanol was slowly added dropwise with stirring. The reaction solution was concentrated under reduced pressure, methanol and toluene were added again, and the solution was concentrated under reduced pressure. This was repeated 4 times, and the obtained colorless solid and triethylamine (3.5 ml, 24.8 mmol) were dissolved in dichloromethane (50 ml) and the mixture was stirred under ice-cooling. Then, ethyl chloroformate (2.2 ml, 22.8 mmol) was added, and the mixture was stood at room temperature overnight. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with diluted hydrochloric acid and saturated brine, and dried over anhydrous magnesium sulfate. The solution was concentrated under reduced pressure, and the obtained oil was purified by silica gel column chromatography (methanol-chloroform) to give the title compound (3.30 g, yield 67%) as a colorless oil.

Workup

  1. stirringThe mixture was stirred at the same temperature for 2.5 hr
  2. temperaturecooled to room temperature
  3. stirringwith stirring
  4. concentrationThe reaction solution was concentrated under reduced pressure, methanol and toluene
  5. additionwere added again
  6. concentrationthe solution was concentrated under reduced pressure
  7. stirringthe mixture was stirred under ice-
  8. temperaturecooling
  9. extractionextracted with ethyl acetate
  10. washThe organic layer was washed with diluted hydrochloric acid and saturated brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. concentrationThe solution was concentrated under reduced pressure
  13. customthe obtained oil was purified by silica gel column chromatography (methanol-chloroform)

Sources & evidence

ORD record
ord-663921d504774e9c877b5c225097902b
Source dataset
uspto-grants-2013_08
Patent number
US08513235B2

Reaction notes

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