Ethylene Glycol → (S)-1-(3-Chloro-phenyl)-2-(3-[1,3]dioxolan-2-yl-2-methoxy-pyridin-4-ylamino)-ethanol

HRID 561958Notes

Reaction equation

[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[C:7]([O:13][CH3:14])=[N:8][CH:9]=[CH:10][C:11]=1I.[NH2:15][CH2:16][C@H:17]([C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=1)[OH:18].C(O)CO.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC(O)C.[Cu]I.CO.C(Cl)Cl>[Cl:25][C:21]1[CH:20]=[C:19]([C@H:17]([OH:18])[CH2:16][NH:15][C:11]2[CH:10]=[CH:9][N:8]=[C:7]([O:13][CH3:14])[C:6]=2[CH:2]2[O:3][CH2:4][CH2:5][O:1]2)[CH:24]=[CH:23][CH:22]=1

Participants

Conditions

Temperature: 75 °C

Procedure

A suspension of 3-[1,3]dioxolan-2-yl-4-iodo-2-methoxy-pyridine (3.07 g, 10.0 mmol), (S)-2-amino-1-(3-chloro-phenyl)-ethanol (1.71 g, 10 mmol), CuI (190 mg, 1.0 mmol), ethylene glycol (1.86 g, 30 mmol) and K3PO4 (6.3 g, 30 mmol) in 2-propanol (200 mL) was sealed and heated at 75° C. for 22 h (CuI and K3PO4 were crushed into powders before added). After cooled down to room temperature, the reaction mixture was loaded on silica gel. The chromatography with eluant CH2Cl2: MeOH=100:1 afforded the title product (1.27 g, 38%). 1H NMR (CDCl3) δ 3.30 (m, 1H) 3.45 (m, 1H), 3.87 (s, 3H), 3.96-4.05 (4H), 4.85 n (m, 1H), 6.09 (s, 1H), 6.15-6.30 (2H), 7.21-7.35 (2H), 7.41 (s, 1H), 7.82 (d, J=6 Hz, 1H). ESI-MS m/z 351.4 (MH+).

Workup

customwas sealed
temperatureAfter cooled down to room temperature

Sources & evidence

ORD record: ord-1e91c1320fe84b10ac66c549c75bd047
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08063225B2

Reaction notes

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