Cesium carbonate → (R)-2-[4-(4-Pyridin-3-yl-phenoxy)-phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 750024Notes

Reaction equation

[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=2)[CH:2]=1.[C:14]([O:18][C:19]([N:21]1[CH2:25][CH2:24][CH2:23][C@@H:22]1[CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31](I)=[CH:30][CH:29]=1)=[O:20])([CH3:17])([CH3:16])[CH3:15].C(=O)([O-])[O-].[Cs+].[Cs+].Cl.CN(C)CC(O)=O>O1CCOCC1.CCOC(C)=O.O>[C:14]([O:18][C:19]([N:21]1[CH2:25][CH2:24][CH2:23][C@@H:22]1[CH2:26][O:27][C:28]1[CH:29]=[CH:30][C:31]([O:13][C:10]2[CH:11]=[CH:12][C:7]([C:3]3[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=3)=[CH:8][CH:9]=2)=[CH:32][CH:33]=1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of product from step 2 (114 mg, 0.66 mmol) in dioxane (2 mL) was added (R)-2-(4-iodo phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (403 mg, 1.0 mmol) in dioxane (1.5 mL) and cesium carbonate (432 mg, 1.33 mmol). The vessel was purged with nitrogen for 15 min before N,N-dimethylglycine hydrochloride (9 mg, 0.06 mmol) in dioxane (0.5mL) and Cu(I) iodide (4 mg, 0.02 mmol) were added. The resulted mixture was stirred at 90° C. for 48 h. It was then diluted with EtOAc and water, organic layer was separate, washed with water, brine, dried over anhydrous MgSO4 and concentrated in vacuo to yellow oil. The crude mixture was purified by silica gel flash chromatography (15% EtOAc/Hexane) to obtain the title product as yellow oil (142 μg, 48%).

Workup

additionwere added
customwas separate
washwashed with water, brine
dry with materialdried over anhydrous MgSO4
concentrationconcentrated in vacuo to yellow oil
customThe crude mixture was purified by silica gel flash chromatography (15% EtOAc/Hexane)

Sources & evidence

ORD record: ord-888f88a243c440c1bf529c104b5c6300
Source dataset: uspto-grants-2008_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07402684B2

Reaction notes

Loading…