Water → (4R,9aR)-6-(3-Methoxy-propyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

HRID 11921Notes

Reaction equation

HRID 11921 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:20][C@@H:19]([CH3:21])[N:18]2[C@H:10]([CH2:11][C:12]3[C:17]2=[N:16][C:15]([CH2:22][CH2:23][CH2:24][OH:25])=[CH:14][CH:13]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:28]I.O>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:20][C@@H:19]([CH3:21])[N:18]2[C@H:10]([CH2:11][C:12]3[C:17]2=[N:16][C:15]([CH2:22][CH2:23][CH2:24][O:25][CH3:28])=[CH:14][CH:13]=3)[CH2:9]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodide2×HCID 24758Sodium hydrideHCID 69556846(4R,9aR)-6-(3-Hydroxy-propyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

Product 1

HCID 69557464(4R,9aR)-6-(3-Methoxy-propyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl esterYield 73.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 160.0 mg (0.46 mmol) (4R,9aR)-6-(3-hydroxy-propyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester in 4 ml tetrahydrofuran was cooled to 0 deg C. and treated with 24.0 mg (0.51 mmol, 60% dispersion in mineral oil) sodium hydride. After 30 min 32 μl (0.51 mmol) methyl iodide was added and the cooling bath was removed. After 6 h another 0.64 μl (1.02 mmol) methyl iodide was added and the reaction was stirred overnight. The reaction mixture was poured into water and was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated on a rotary evaporator. The residue was purified by chromatography on silica gel (0.032–0.063 mm) with ethyl acetate:n-hexane (1:4) as eluant to afford the desired compound as a colorless oil (73.9%).

Workup

  1. customthe cooling bath was removed
  2. extractionwas extracted three times with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated on a rotary evaporator
  7. customThe residue was purified by chromatography on silica gel (0.032–0.063 mm) with ethyl acetate:n-hexane (1:4) as eluant

Sources & evidence

ORD record
ord-660832ee65134c9f8989cfb890244cdf
Source dataset
uspto-grants-2006_08
Patent number
US07098337B2

Reaction notes

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