Trifluoroacetic acid → 3-(Pyridin-4-yl)-3,9-diazaspiro[5.5]undecane
Reaction equation
C(O)(C(F)(F)F)=O.[N:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH2:31][CH2:30][C:17]3([CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18]3)[CH2:16][CH2:15]2)=[CH:10][CH:9]=1>C(Cl)Cl>[N:8]1[CH:9]=[CH:10][C:11]([N:14]2[CH2:31][CH2:30][C:17]3([CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)[CH2:16][CH2:15]2)=[CH:12][CH:13]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
Sodium tert-butylate (4 mmol) was added to a solution of 4-bromopyridine hydrochloride (1.9 mmol) in dry toluene (10 ml) under argon, followed by 3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (1.6 mmol) in toluene (5 ml). Argon was added to the mixture for 15 min, then (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.123 mmol) and tris(dibenzylidene acetone)dipalladium (0.041 mmol) were added. The mixture was heated at 90° C. for 4 h and the reaction progress was monitored by thin-layer chromatography. On completion of the reaction the mixture was diluted with ethyl acetate (100 ml) and extracted with water and saturated sodium chloride solution, dried (Na2SO4), filtered and concentrated to small volume. The crude product was purified by column chromatography (3% methanol in DCM). Yield: 45% 2. TFA (13 eq.) was added to a DCM solution (10 ml/mmol) of tert-butyl 9-(pyridin-4-yl)-3,9-diazaspiro[5.5]undecane-3-carboxylate (1 eq.) at 0° C. and the mixture was stirred for 2 h at RT. The solvent was removed and the product was dried under vacuum. The crude product was used in the following stage with no further purification. Yield: quantitative
Workup
- customThe solvent was removed
- customthe product was dried under vacuum
- customThe crude product was used in the following stage with no further purification
Sources & evidence
- ORD record
- ord-e7c25fbf61914c16ab30d0a1766aea72
- Source dataset
- uspto-grants-2012_04
- Patent number
- US08158628B2
Reaction notes
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