Water → HCID 9945506, compound

HRID 397325Notes

Reaction equation

HRID 397325 reaction equation
[H-].[Na+].C(OC(=O)[NH:9][C@@H:10]([CH3:25])[CH2:11][C:12]1[C:20]2[CH:19]=[C:18]([OH:21])[CH:17]=[CH:16][C:15]=2[N:14]2[CH2:22][CH2:23][CH2:24][C:13]=12)(C)(C)C.Br[CH2:28][CH2:29][O:30][CH2:31][CH2:32][O:33][CH3:34].O>CN(C)C=O.C(OCC)(=O)C>[CH3:34][O:33][CH2:32][CH2:31][O:30][CH2:29][CH2:28][O:21][C:18]1[CH:17]=[CH:16][C:15]2[N:14]3[CH2:22][CH2:23][CH2:24][C:13]3=[C:12]([CH2:11][C@@H:10]([NH2:9])[CH3:25])[C:20]=2[CH:19]=1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 1235321-Bromo-3,6-dioxaheptaneHCID 69364305HCID 69364305, compound

Product 1

HCID 9945506HCID 9945506, compoundYield 49.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

25 mg sodium hydride 55-65% in oil was added to a solution of 165 mg (S)-[2-(6-hydroxy-2,3-dihydro-1H-3a-aza-cyclopenta[a]inden-8-yl)-1-methyl-ethyl]-carbamic acid tert-butyl ester in 1.5 mL N,N-dimethylformamide. The mixture was stirred at room temperature for 30 min, then 122 mg 1-bromo-2-(2-methoxyethoxy)-ethane was added to the mixture and the mixture was stirred at room temperature for an additional 7 h. The reaction mixture was distributed between water and ethyl acetate. The phases were separated, the organic phase is washed with water, 10% citric acid, 10% sodium bicarbonate and brine, dried over magnesium sulfate and evaporated. The residue was purified by chromatography on silica gel with hexane:ethyl acetate=4:1. The product fractions were evaporated and the residue taken up in 1.5 mL of a 2.16 M solution of hydrochloric acid in ethyl acetate. The mixture was stirred at room temperature for 3 h. The solid was collected by filtration, neutralised with aqueous ammonium hydroxide and purified by chromatography on silica gel with dichloromethane:methanol:aqueous ammonium hydroxide=90:9:1. The product fractions are dried over magnesium sulfate and evaporated to yield 82 mg (S)-2-{6-[2-(2-methoxy-ethoxy)-ethoxy]-2,3-dihydro-1H-3a-aza-cyclopenta[a]inden-8-yl}-1-methyl-ethylamine as light brown oil. MS: M+H=333.3; M+H−NH3=316.3.

Workup

  1. stirringthe mixture was stirred at room temperature for an additional 7 h
  2. customThe phases were separated
  3. washthe organic phase is washed with water, 10% citric acid, 10% sodium bicarbonate and brine
  4. dry with materialdried over magnesium sulfate
  5. customevaporated
  6. customThe residue was purified by chromatography on silica gel with hexane
  7. customThe product fractions were evaporated
  8. stirringThe mixture was stirred at room temperature for 3 h
  9. filtrationThe solid was collected by filtration
  10. custompurified by chromatography on silica gel with dichloromethane
  11. dry with materialThe product fractions are dried over magnesium sulfate
  12. customevaporated

Sources & evidence

ORD record
ord-ac50cc9e5eba4396bb808ed674c2488b
Source dataset
uspto-grants-2003_08
Patent number
US06610685B2

Reaction notes

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