Ethylene Glycol → (R)-1-[2-(5,5-Dimethyl-[1,3]dioxan-2-yl)-4-methoxy-3-methoxymethoxy-phenylamino]-3-(2,4-dimethyl-phenoxy)-propan-2-ol

HRID 929112Notes

Reaction equation

Br[C:2]1[C:7]([CH:8]2[O:13][CH2:12][C:11]([CH3:15])([CH3:14])[CH2:10][O:9]2)=[C:6]([O:16][CH2:17][O:18][CH3:19])[C:5]([O:20][CH3:21])=[CH:4][CH:3]=1.[NH2:22][CH2:23][C@@H:24]([OH:35])[CH2:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][C:28]=1[CH3:34].C(O)CO.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC(O)C.[Cu]I>[CH3:14][C:11]1([CH3:15])[CH2:12][O:13][CH:8]([C:7]2[C:6]([O:16][CH2:17][O:18][CH3:19])=[C:5]([O:20][CH3:21])[CH:4]=[CH:3][C:2]=2[NH:22][CH2:23][C@@H:24]([OH:35])[CH2:25][O:26][C:27]2[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][C:28]=2[CH3:34])[O:9][CH2:10]1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 2-(6-bromo-3-methoxy-2-methoxymethoxy-phenyl)-5,5-dimethyl-[1,3]dioxane (36 mg, 0.1 mmol), (R)-1-amino-3-(2,4-dimethyl-phenoxy)-propan-2-ol (30 mg, 0.15 mmol), CuI (51.4 mg, 0.27 mmol), ethylene glycol (168 mg, 2.7 mmol), and K3PO4 (573 mg, 2.7 mmol) in 2-propanol (8 mL) was heated at 90° C. in a sealed vial for 14 h and evaporated. Chromatography of the residue with hexanes and EtOAc afforded the title compound (305 mg, 71%). 1H NMR (CDCl3) δ 0.79 (s, 3H, CH3), 1.29 (s, 3H, CH3), 2.21 (s, 3H, CH3), 2.25 (s, 3H, CH3), 2.95 (br s, 1H, OH), 3.30 (m, 1H), 3.49 (s, 3H, OCH3), 3.51 (m, 1H), 3.65 (m, 2H), 3.75 (s, 3H, OCH3), 3.77 (m, 2H), 4.00 (m, 2H), 4.25 (m, 1H), 5.09 (s, 2H), 6.05 (s, 1H), 6.48 (d, J=8 Hz, 1H), 6.69 (d, J=8 Hz, H), 6.82 (d, J=8 Hz, 1H), 6.92 (d, J=8 Hz, 1H), 6.95 (s, 1H). ESI-MS m/z 476.8 (MH+).

Workup

customevaporated

Sources & evidence

ORD record: ord-128ae7286e024a1bb17ded76462d8277
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09290503B2

Reaction notes

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