Acetylcholine → N-[2-[N-ethyl-N-[2-(2-fluoropyridin-3-yloxy)ethyl]amino]ethyl]phthalimide

HRID 2273615Notes

Reaction equation

HRID 2273615 reaction equation
[CH2:1]([N:3]([CH2:7][CH2:8][N:9]1[C:13](=[O:14])[C:12]2=[CH:15][CH:16]=[CH:17][CH:18]=[C:11]2[C:10]1=[O:19])[CH2:4][CH2:5][OH:6])[CH3:2].[F:20][C:21]1[C:26](O)=[CH:25][CH:24]=[CH:23][N:22]=1.C1[C@@H](COC2C=CC=NC=2[18F])NC1.C(OCC[N+](C)(C)C)(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[CH2:1]([N:3]([CH2:7][CH2:8][N:9]1[C:13](=[O:14])[C:12]2=[CH:15][CH:16]=[CH:17][CH:18]=[C:11]2[C:10]1=[O:19])[CH2:4][CH2:5][O:6][C:26]1[C:21]([F:20])=[N:22][CH:23]=[CH:24][CH:25]=1)[CH3:2]

Participants

8

Reactant 6

HCID 187AcetylcholineHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 4508602-Fluoro-3-(2S-azetidinylmethoxy)pyridine, F-18HCID 27627852-Fluoro-3-hydroxypyridineHCID 52951944N-[2-[N-ethyl-N-(2-hydroxyethyl)amino]ethyl]phthalimide

Product 1

HCID 52951945N-[2-[N-ethyl-N-[2-(2-fluoropyridin-3-yloxy)ethyl]amino]ethyl]phthalimideYield 79%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of compound 3 (1.65 g, 6.29 mmol) in anhydrous tetrahydrofuran (THF, 80 mL) were successively added, under argon, 2-fluoro-3-hydroxypyridine (0.72 g, 6.37 mmol) (Dollé, F.; Valette, H.; Bottlaender, M.; Hinnen, F.; Vaufrey, F.; Guenther, I.; Crouzel, C. Synthesis of 2-[18F]fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine, a highly potent radioligand for in vivo imaging central nicotinic acetylcholine receptors. J. Label. Compds. Radiopharm. 1998, 41, 451-463), triphenylphosphine (1.65 g, 6.29 mmol) and dropwise diisopropyl azodicarboxylate (DIAD, 1.71 mL, 8.68 mmol). The mixture was stirred at room temperature for 24 h. The solvent was evaporated under reduced pressure and the residue was chromatographed (Al2O3, AcOEt) to give compound 4 (1.77 g, 4.95 mmol) as a yellow solid. Yield 79%; Rf (Al2O3, AcOEt) 0.84; mp 58-60° C.; IR (KBr) ν 1192, 1240, 1290, 1395, 1452, 1712, 2847, 2943 cm−1; 1H NMR (200 MHz, CDCl3) δ 1.29 (t, 3H, J=7.1 Hz), 2.97 (q, 2H, J=7.1 Hz), 3.14 (t, 2H, J=6.5 Hz), 3.24 (t, 2H, J=5.9 Hz), 4.08 (t, 2H, J=6.5 Hz), 4.31 (t, 2H, J=5.9 Hz), 7.35 (ddd, 1H, 5JH-F=0.9 Hz, J=4.8, 7.8 Hz), 7.52 (ddd, 1H, 4JH-F=10.0 Hz, J=1.6, 7.8 Hz), 7.97 (m, 3H), 8.07 (m, 2H); MS m/z 357 (M+, 1), 231 (15), 197 (100), 174 (23), 130 (10), 85 (17), 76 (10), 57 (45).

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. customthe residue was chromatographed (Al2O3, AcOEt)

Sources & evidence

ORD record
ord-9f1c188c56cc4f6784d9e45f805022a9
Source dataset
uspto-grants-2015_09
Patent number
US09125937B2

Reaction notes

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