2,7-Dibromo-9-fluorenone → 2-[N-Boc-3,7-diazabicyclo[3.3.0]octan-3-yl]-7-bromofluoren-9-one

HRID 553038Notes

Reaction equation

HRID 553038 reaction equation
[C:1]([N:8]1[CH2:15][CH:14]2[CH:10]([CH2:11][NH:12][CH2:13]2)[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[Br:16][C:17]1[CH:29]=[CH:28][C:27]2[C:26]3[C:21](=[CH:22][C:23](Br)=[CH:24][CH:25]=3)[C:20](=[O:31])[C:19]=2[CH:18]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([N:8]1[CH2:9][CH:10]2[CH:14]([CH2:13][N:12]([C:23]3[CH:24]=[CH:25][C:26]4[C:27]5[C:19](=[CH:18][C:17]([Br:16])=[CH:29][CH:28]=5)[C:20](=[O:31])[C:21]=4[CH:22]=3)[CH2:11]2)[CH2:15]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

7

Reactant 3

HCID 2599222,7-Dibromo-9-fluorenoneHCID 4142526Tert-butyl octahydropyrrolo(3,4-c)pyrrole-2-carboxylateHCID 23676156Sodium t-butoxide

Product 1

HCID 671640772-[N-Boc-3,7-diazabicyclo[3.3.0]octan-3-yl]-7-bromofluoren-9-oneYield 75.5%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 3-Boc-3,7-diazabicyclo[3.3.0]octane (2.12 g, 10.0 mmol; see WO 0181347), 2,7-dibromofluoren-9-one (6.76 g, 20.0 mmol; Aldrich), tris(dibenzylideneacetone)dipalladium (0) (Pd2 dba3; 185 mg, 0.202 mmol; Strem), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP; 310 mg, 0.498 mmol; Strem) and sodium tert-butoxide (1.4 g, 14.6 mmol; Aldrich) in 100 mL toluene was warmed to 85° C. and stirred for 9 h. The reaction mixture was cooled to ambient temperature and filtered through diatomaceous earth, rinsing with dichloromethane. After concentrating the solution under reduced pressure, the residue was purified by column chromatography (silica gel, 10-60% EtOAc/hexanes) to give the title compound (3.54 g, 7.55 mmol, 75% yield). MS (DCI/NH3): m/z 469, 471 (M+1)+.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. filtrationfiltered through diatomaceous earth
  3. washrinsing with dichloromethane
  4. concentrationAfter concentrating the solution under reduced pressure
  5. customthe residue was purified by column chromatography (silica gel, 10-60% EtOAc/hexanes)

Sources & evidence

ORD record
ord-54fe8004448142798cd6706e112a0a5b
Source dataset
uspto-grants-2011_05
Patent number
US07951791B2

Reaction notes

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