RSS-Feed abonnieren
DOI: 10.1055/s-2006-947316
Synthesis of (Fluoroalkyl)amines by Deoxyfluorination of Amino Alcohols
Publikationsverlauf
Publikationsdatum:
04. Juli 2006 (online)
![](https://www.thieme-connect.de/media/synlett/200611/lookinside/thumbnails/10.1055-s-2006-947316-1.jpg)
Abstract
Deoxyfluorination of amino alcohols was achieved using N,N-diethyl-α,α-difluorobenzylamine (DFBA) to furnish N-benzoyl(fluoroalkyl)amines selectively.
Key words
amino alcohols - fluorination - deoxygenation - substitution - N,N-diethyl-α,α-difluorobenzylamine
-
1a
Coutts RT.Benderly A.Mak ALC. J. Fluorine Chem. 1980, 16: 277 -
1b
Kozikowski AP.Wu J.-P. Tetrahedron Lett. 1990, 31: 4309 -
1c
Schumacher DP.Clark JE.Murphy BL.Fischer PA. J. Org. Chem. 1990, 55: 5291 -
1d
Dolensky B.Kirk KL. J. Org. Chem. 2001, 66: 4687 -
1e
Grunewald GL.Romero FA.Criscione KR. J. Med. Chem. 2005, 48: 1806 -
2a
Fluorine-Containing Amino Acids
Kukhar VP.Soloshonok VA. Wiley; Chichester: 1995. -
2b
Qiu X.-L.Meng W.-D.Qing F.-L. Tetrahedron 2004, 60: 6711 ; and references cited therein -
3a
Chi DY.Kilbourn MR.Katzenellenbogen JA.Welch MJ. J. Org. Chem. 1987, 52: 658 -
3b
Lyle TA.Magill CA.Pitzenberger SM. J. Am. Chem. Soc. 1987, 109: 7890 -
3c
Posakony JJ.Tewson TJ. Synthesis 2002, 766 -
3d
Bolton R. J. Labelled Compd. Radiopharm. 2002, 45: 485 -
3e
Couturier O.Luxen A.Chatal J.-F.Vuillez J.-P.Rigo P.Hustinx R. Eur. J. Nucl. Med. Mol. Imaging 2004, 31: 1182 -
4a
White GJ.Garst ME. J. Org. Chem. 1991, 56: 3177 -
4b
Van Dort ME.Jung Y.-W.Sherman PS.Kilbourn MR.Wieland DM. J. Med. Chem. 1995, 38: 810 -
4c
Ok D.Fisher MH.Wyvratt MJ.Meinke PT. Tetrahedron Lett. 1999, 40: 3831 -
4d
Posakony JJ.Grierson JR.Tewson TJ. J. Org. Chem. 2002, 67: 5164 -
4e
Posakony JJ.Tewson TJ. Synthesis 2002, 766 -
4f
McConathy J.Martarello L.Malveaux EJ.Camp VM.Simpson NE.Simpson CP.Bowers GD.Olson JJ.Goodman MM. J. Med. Chem. 2002, 45: 2240 -
6a
Silverman RB.Levy MA. J. Org. Chem. 1980, 45: 815 -
6b
Remuzon P.Bouzard D.Di Cesare P.Essiz M.Jacquet JP.Kiechel JR.Ledoussal B.Kesseler RE.Fung-Tomc J. J. Med. Chem. 1991, 34: 29 -
6c
Jonghe SD.Overmeire IV.Calenbergh SV.Hendrix C.Busson R.Keukeleire DD.Herdewijn P. Eur. J. Org. Chem. 2000, 3177 - 7
Ye C.Shreeve JM. J. Fluorine Chem. 2004, 125: 1869 -
8a
Kobayashi S.Yoneda A.Fukuhara T.Hara S. Tetrahedron Lett. 2004, 45: 1287 -
8b
Kobayashi S.Yoneda A.Fukuhara T.Hara S. Tetrahedron 2004, 60: 6923 - 9
Yoneda A.Fukuhara T.Hara S. Chem. Commun. 2005, 3589 - 10
Furuya T.Fukuhara T.Hara S. J. Fluorine Chem. 2005, 126: 721 - 11
Yu H.-W.Nakano Y.Fukuhara T.Hara S. J. Fluorine Chem. 2005, 126: 962 - 13
Stewart WE.Siddall TH. Chem. Rev. 1970, 70: 517 - 15
Charvillon FB.Amouroux R. Tetrahedron Lett. 1996, 37: 5103
References and Notes
The half-life of 18F is about 110 min.
12Due to the enolizable character of the amide function,13 the NMR spectra of the N-acylated products 2 were sometimes complicated and reduction of the amide function to the amine was necessary for analysis. When DFBA was used for the reaction with N-benzylamino alcohols, N,N-dibenzylamine derivatives were formed after the reduction, and their NMR spectra are simpler than that of the product from DFMBA. Therefore, DFBA was used instead of DFMBA. DFBA showed reactivity comparable with DFMBA and can be prepared from N,N-diethylbenzamide as DFMBA.10
14To a reactor with a TeflonTM PFA tube with a diameter of 10 mm sealed at one end, 1a (137 mg, 1 mmol) and DFBA (478 mg, 2.4 mmol) were introduced. The open end of the reactor was connected to a reflux condenser. Then, the reactor part was submitted to microwave-irradiation (IDX microwave oven for organic synthesis IMCR-25003) for 10 min and during the irradiation the temperature was kept at 70 °C. After cooling, the reaction mixture was poured into an aq solution of NaHCO3. The product was extracted with Et2O (3 ×) and the combined ethereal layers were dried over MgSO4. Purification by column chromatography (silica gel, hexane-Et2O) gave 2a (207 mg, 0.85 mmol) in 85% yield. N -(2-Fluoroethyl)- N -phenylbenzamide ( 2a): IR (neat): 1649, 1494, 1377 cm-1. 1H NMR: δ = 7.32-7.09 (m, 10 H), 4.76 (dt, J = 47.6, 4.9 Hz, 2 H), 4.20 (dt, J = 25.6, 4.9 Hz, 2 H). 19C NMR: δ = 170.94, 144.08, 135.80, 129.94, 129.31 (2 C), 128.90 (2 C), 127.89 (2 C), 127.83 (2 C), 126.91, 81.52 (d, J = 168.7 Hz), 51.57 (d, J = 20.7 Hz). 19F NMR: δ = -222.60 to -222.98 (m, 1 F). HRMS (EI): m/z calcd for C15H14NOF: 243.1059; found: 243.1057. ( S )-1-Fluoro-2-aminopropane Hydrochloride ( S )-(5)·HCl: White solid; mp 123-124 °C (lit.4e 127-127.5 °C); [α]D 21 +12.4 (c 1.01, MeOH) {lit.4e [α]D 23 +12.7 (c 1.01, MeOH)}. (R)-MTPA amide of ( S )-5 19F NMR: δ = -69.54 (s, 3 F), -232.36 (dt, J = 26.2, 47.0 Hz, 1 F). ( R )-1-Fluoro-2-aminopropane Hydrochloride ( R )-(5)·HCl: White solid; mp 123-124.5 °C (lit.4e 127-128 °C); [α]D 22 -13.7 (c 1.00, MeOH) {lit.4e [α]D 23 -14.9 (c 1.10, MeOH)}. (R)-MTPA amide of ( R )-5; 19F NMR: δ = -69.47 (s, 3 F), -232.73 (dt, J = 26.2, 47.0 Hz, 1 F).