Biphenyl → 5-Thiazol-2-yl-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

HRID 1038032

Reaction equation

HRID 1038032 reaction equation
Br[C:2]1[S:3][CH:4]=[CH:5][N:6]=1.CC(C)([O-])C.[Na+].[C:13]([O:17][C:18]([N:20]1[CH2:25][C@@H:24]2[CH2:26][C@H:21]1[CH2:22][NH:23]2)=[O:19])([CH3:16])([CH3:15])[CH3:14].C1(C2C=CC=CC=2)C=CC=CC=1>O1CCOCC1.C(OCC)(=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH:24]2[CH2:26][CH:21]1[CH2:22][N:23]2[C:2]1[S:3][CH:4]=[CH:5][N:6]=1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

9

Reactant 4

HCID 7095BiphenylHCID 764302-BromothiazoleHCID 11521263(1S,4S)-2-Boc-2,5-diazabicyclo[2.2.1]heptaneHCID 23676156Sodium t-butoxide

Product 1

HCID 669396205-Thiazol-2-yl-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl esterYield 52%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2-bromothiazole (200 mg, 1.22 mmol), palladium acetate (15 mg, 0.06 mmol), sodium tert-butoxide (217 mg, 2.26 mmol), (S,S) 2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (280 mg, 1.4 mmol) and 2-Di-t-butylphosphino)-biphenyl (37 mg, 0.118 mmol) was stirred in dioxane (10 ml) at 80° C. for overnight. The reaction was cooled, diluted with ethyl acetate (40 ml) and H2O (50 ml). The organic layer was separated, dried (Na2SO4), filtered and solvent evaporated. The residue was purified by chromatography eluting with 5% MeOH/DCM yielding product as a white solid. (180 mg, 52% yield)

Workup

  1. temperatureThe reaction was cooled
  2. customThe organic layer was separated
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customsolvent evaporated
  6. customThe residue was purified by chromatography
  7. washeluting with 5% MeOH/DCM yielding product as a white solid

Sources & evidence

ORD record
ord-5f0d31b3dc66434a9d00699ec56389b2
Source dataset
uspto-grants-2013_10
Patent number
US08546404B2

Linked notes

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