Cesium carbonate → HCID 66855068, compound

HRID 252106Notes

Reaction equation

[C:1]([O:5][C:6](=[O:13])[NH:7][C@H:8]1[CH2:12][CH2:11][NH:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].Br[C:15]1[CH:16]=[CH:17][C:18]([F:21])=[N:19][CH:20]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1>[C:1]([O:5][C:6](=[O:13])[NH:7][C@H:8]1[CH2:12][CH2:11][N:10]([C:15]2[CH:20]=[N:19][C:18]([F:21])=[CH:17][CH:16]=2)[CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 110 °C

Procedure

Dissolve (S)-pyrrolidin-3-yl-carbamic acid tert-butyl ester (1.49 g, 8 mmol) in toluene (20 mL). Heat to 110° C. and add 5-bromo-2-fluoropyridine (824 μL, 8 mmol), cesium carbonate (3.9 g, 12 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (748 mg, 1.2 mmol) and tris(dibenzylidineacetone)dipalladium(0) (733 mg, 0.8 mmol). Place a nitrogen inlet and condenser on the flask and heat at reflux overnight. Cool and filter the reaction mixture through a pad of Celite® and wash the pad with dichloromethane. Concentrate and chromatograph twice on silica gel, eluting with 0:100 to 25:75 ethyl acetate:dichloromethane, then 10:90 to 40:60 ethylacetate:hexanes, to give (S)-[1-(6-fluoropyridin-3-yl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester as a brown solid (1.54 g, 68%).

Workup

temperatureheat
temperatureat reflux overnight
temperatureCool
filtrationfilter the reaction mixture through a pad of Celite®
washwash the pad with dichloromethane
concentrationConcentrate
washchromatograph twice on silica gel, eluting with 0:100 to 25:75 ethyl acetate

Sources & evidence

ORD record: ord-f9244ccee72e4d7c850299349bfbf1b3
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07868014B2

Reaction notes

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