2,7-Dibromo-9-fluorenone → 3-(7-Bromo-9-oxo-9H-fluoren-2-yl)-(1R,5R)-3,6-diazabicyclo[3.2.0]heptane-6-carboxylic acid tert-butyl ester

HRID 902988Notes

Reaction equation

HRID 902988 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH:13]2[CH:9]1[CH2:10][NH:11][CH2:12]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:15][C:16]1[CH:28]=[CH:27][C:26]2[C:25]3[C:20](=[CH:21][C:22](Br)=[CH:23][CH:24]=3)[C:19](=[O:30])[C:18]=2[CH:17]=1.CC(C)([O-])C.[Na+].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>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]>[C:1]([O:5][C:6]([N:8]1[CH2:14][C@@H:13]2[C@@H:9]1[CH2:10][N:11]([C:22]1[CH:23]=[CH:24][C:25]3[C:26]4[C:18](=[CH:17][C:16]([Br:15])=[CH:28][CH:27]=4)[C:19](=[O:30])[C:20]=3[CH:21]=1)[CH2:12]2)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 2599222,7-Dibromo-9-fluorenoneHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 467381813,6-Diaza-bicyclo(3.2.0)heptane-6-carboxylic acid tert-butyl ester

Product 1

HCID 671635653-(7-Bromo-9-oxo-9H-fluoren-2-yl)-(1R,5R)-3,6-diazabicyclo[3.2.0]heptane-6-carboxylic acid tert-butyl esterYield 58.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 3,6-diazabicyclo[3.2.0]heptane-6-carboxylic acid tert-butyl ester (600 mg, 3.0 mmol; prepared according to patent WO2001081347), 2,7-dibromo-fluoren-9-one (1.3 g, 4 mmol; Aldrich), sodium tert-butoxide (400 mg, 4.2 mmol; Aldrich), tris(dibenzylideneacetone)dipalladium (Pd2(dba)3; 160 mg, 0.17 mmol; Alfa) and racemic 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP; 330 mg, 0.53 mmol; Strem) in dry toluene (30 mL) was warmed to 85° C. and stirred under nitrogen atmosphere for 3 h. The reaction mixture was concentrated under vacuum and purified by flash chromatography (80 g silica gel, 40:60 hexanes-EtOAc) to afford the title compound (800 mg, 1.76 mmol; 55% yield): 1H NMR (300 MHz, CD3OD) δ ppm 7.56-7.61 (2H, m), 7.47 (1H, d, J=8 Hz), 7.38 (1H, d, J=8 Hz), 7.06 (1H, d, J=3 Hz), 6.92 (1H, dd, J=8, 3 Hz), 4.60-4.67 (1H, m), 3.91-4.16 (2H, m), 3.73-3.86 (1H, m), 3.55-3.66 (1H, m), 3.41-3.51 (1H, m), 2.90-3.27 (3H, m), 1.36-1.55 (9H, s); MS (DCl/NH3): m/z 455 (M+1)+, 457 (M+3)+.

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. custompurified by flash chromatography (80 g silica gel, 40:60 hexanes-EtOAc)

Sources & evidence

ORD record
ord-c232a1e5921c4ce99fa9741c7f2d68e7
Source dataset
uspto-grants-2008_04
Patent number
US07365193B2

Reaction notes

Loading…