2-Pentanone, 5-chloro- → (4R,9aR)-6-(4-Chloro-1-(RS)-hydroxy-1-methyl-butyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

HRID 11955

Reaction equation

HRID 11955 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](Br)=[CH:14][CH:13]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Li])(C)(C)C.[Cl:28][CH2:29][CH2:30][CH2:31][C:32](=[O:34])[CH3:33]>C(OCC)C>[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]([C:32]([OH:34])([CH3:33])[CH2:31][CH2:30][CH2:29][Cl:28])=[CH:14][CH:13]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 799932-Pentanone, 5-chloro-HCID 86590113(4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl esterHCID 178418306HCID 178418306, compound

Product 1

HCID 69557408(4R,9aR)-6-(4-Chloro-1-(RS)-hydroxy-1-methyl-butyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl esterYield 50.9%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

A solution of 0.30 g (0.81 mmol) (4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester in 20 ml diethyl ether was cooled to −100 deg C. and treated dropwise with 65 μl (0.97 mmol) tert-butyllithium (1.5 M solution in n-pentane). After 15 min, 0.12 g (0.11 ml, 0.98 mmol) 5-chloro-2-pentanone was added, the temperature was allowed to rise to −75 deg C. and after an additional 15 min, the reaction was quenched with 10%. aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The solvent was removed on a rotary evaporator and the residue was chromatographed on silica gel (0.032–0.063 mm) with ethyl acetate:n-hexane (1:2) as eluant to afford the compound as a colorless oil (50.9%).

Workup

  1. customto rise to −75 deg C
  2. waitand after an additional 15 min
  3. customthe reaction was quenched with 10%
  4. extractionaqueous ammonium chloride solution and extracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customThe solvent was removed on a rotary evaporator
  9. customthe residue was chromatographed on silica gel (0.032–0.063 mm) with ethyl acetate:n-hexane (1:2) as eluant

Sources & evidence

ORD record
ord-17b941eede84488b9e92575473d7bd1b
Source dataset
uspto-grants-2006_08
Patent number
US07098337B2

Linked notes

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