Methyl Ethyl Ketone → (3aSR,10RS)-2-(2-Bromoethyl)-6-(1,1-difluoro-methoxy)-10-(3-hydroxy-phenyl)-3a-methyl-3a,4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta[b]fluorene-1,3-dione

HRID 41035Notes

Reaction equation

HRID 41035 reaction equation
CO[C:3]([C:5]1([CH3:29])[CH2:17][C:16]2[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([O:18][CH:19]([F:21])[F:20])[CH:14]=3)[NH:9][C:8]=2[CH:7]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([OH:28])[CH:23]=2)[NH:6]1)=[O:4].[Br:30][CH2:31][CH2:32][N:33]=[C:34]=[O:35].C(=O)(O)[O-].[Na+].[CH3:41][C:42](=[O:45])[CH2:43]C>>[CH:5]([O:45][CH:42]([CH3:43])[CH3:41])([CH3:17])[CH3:3].[Br:30][CH2:31][CH2:32][N:33]1[C:34](=[O:35])[N:6]2[CH:7]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([OH:28])[CH:23]=3)[C:8]3[NH:9][C:10]4[C:15]([C:16]=3[CH2:17][C:5]2([CH3:29])[C:3]1=[O:4])=[CH:14][C:13]([O:18][CH:19]([F:21])[F:20])=[CH:12][CH:11]=4

Participants

6

Reactant 4

HCID 6569Methyl Ethyl KetoneHCID 516892Sodium BicarbonateHCID 42559572-Bromoethyl isocyanateHCID 68885053(1RS,3SR)-6-(1,1-difluoro-methoxy)-1-(3-hydroxy-phenyl)-3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester

Product 2

HCID 7914Diisopropyl EtherHCID 68939720(3aSR,10RS)-2-(2-Bromoethyl)-6-(1,1-difluoro-methoxy)-10-(3-hydroxy-phenyl)-3a-methyl-3a,4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta[b]fluorene-1,3-dioneYield 61%

Procedure

To a solution of 5.5 mg (1RS,3SR)-6-(1,1-difluoro-methoxy)-1-(3-hydroxy-phenyl)-3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester in 10 ml 2-butanon are added 132 μl bromoethyl isocyanate. The mixture is heated to reflux for 30 h. An aqueous solution of sodium bicarbonate is added and the mixture is extracted with ethyl acetate. The organic layer is washed with brine and dried with magnesium sulfate. The solvent is removed at reduced pressure. After column chromatography (silica gel; toluene, ethyl acetate 4:1) and trituration with diisopropylether, 550 mg (61%) of the title compound are obtained as a colorless solid. MS: m/z (MH+)=519.9/522.0

Workup

  1. temperatureThe mixture is heated
  2. temperatureto reflux for 30 h
  3. extractionthe mixture is extracted with ethyl acetate
  4. washThe organic layer is washed with brine
  5. dry with materialdried with magnesium sulfate
  6. customThe solvent is removed at reduced pressure

Sources & evidence

ORD record
ord-67c7abd4874a426fa289446e4dbf13c5
Source dataset
uspto-grants-2013_09
Patent number
US08530493B2

Reaction notes

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