Tetrahydrofuran → HCID 11997507, compound

HRID 1985718Notes

Reaction equation

HRID 1985718 reaction equation
C(OC([N:8]1[CH2:20][C@@H:19]2[N:11]([C:12]3[N:13]=[C:14]4[CH2:23]OC(=O)[C:15]4=[CH:16][C:17]=3[CH2:18]2)[C@H:10]([CH3:25])[CH2:9]1)=O)(C)(C)C.[CH3:26][Mg]Br.[O:29]1[CH2:33][CH2:32]CC1>C(OCC)C>[CH3:26][C:33]1([CH3:32])[C:15]2=[CH:16][C:17]3[CH2:18][C@H:19]4[N:11]([C:12]=3[N:13]=[C:14]2[CH2:23][O:29]1)[C@H:10]([CH3:25])[CH2:9][NH:8][CH2:20]4

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 67237126HCID 67237126, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 11997507HCID 11997507, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 0.345 g (5R,8aR)-5-methyl-1-oxo-3,5,6,8,8a,9-hexahydro-1H-2-oxa-4,4b,7-triaza-cyclopenta[b]fluorene-7-carboxylic acid tert-butyl ester in 5 ml tetrahydrofuran was added at 0° C. 2.00 ml of a 2M solution of methylmagnesium bromide in diethyl ether. The mixture was stirred at 0° C. for 30 min and at room temperature for 1 h. The reaction mixture was partitioned between 10% aqueous ammonium chloride and ethyl acetate, the phases were separated and the organic phase was washed with 10% aqueous citric acid 10% aqueous sodium bicarbonate and brine dried over sodium sulfate and evaporated. The residue was taken up in 5 ml trifluoroacetic acid and kept at room temperature for 2 h. The solvent was evaporated and the residue was partitioned between water and ethyl acetate. The phases were separated and the aqueous phase was mixed with dichloromethane. The pH of the mixture was adjusted to 12.00 by addition of 2N aqueous sodium hydroxide. The phases were separated and the organic phase was washed with half concentrated brine dried over sodium sulfate and evaporated. The residue was purified by chromatography on silica gel with dichloromethane:methanol:ammonia; 90:10:1 to yield 0.18 g of the title compound as slightly yellow oil (MS: 260.2 (M+H+))

Workup

  1. customThe reaction mixture was partitioned between 10% aqueous ammonium chloride and ethyl acetate
  2. customthe phases were separated
  3. washthe organic phase was washed with 10% aqueous citric acid 10% aqueous sodium bicarbonate and brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated
  6. waitkept at room temperature for 2 h
  7. customThe solvent was evaporated
  8. customthe residue was partitioned between water and ethyl acetate
  9. customThe phases were separated
  10. additionthe aqueous phase was mixed with dichloromethane
  11. additionThe pH of the mixture was adjusted to 12.00 by addition of 2N aqueous sodium hydroxide
  12. customThe phases were separated
  13. washthe organic phase was washed with half concentrated brine
  14. dry with materialdried over sodium sulfate
  15. customevaporated
  16. customThe residue was purified by chromatography on silica gel with dichloromethane

Sources & evidence

ORD record
ord-eedce3d80f9a48faa3829fa9c80f83a6
Source dataset
uspto-grants-2009_06
Patent number
US07547699B2

Reaction notes

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