Cesium carbonate → HCID 66875433, compound

HRID 1666517Notes

Reaction equation

[OH:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=1)[CH:5]=[C:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1.Br[C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][N:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC#N.CC#N.CC#N.CC#N.F[P-](F)(F)(F)(F)F.[Cu+]>[C:15]([O:14][C:12]([N:9]1[CH2:8][CH2:7][C:6](=[CH:5][C:4]2[CH:19]=[CH:20][CH:21]=[C:2]([O:1][C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][N:24]=3)[CH:3]=2)[CH2:11][CH2:10]1)=[O:13])([CH3:18])([CH3:16])[CH3:17]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of tert-butyl-4-(3-hydroxybenzylidene)piperidine-1-carboxylate (0.500 g; Example 57, Step 3), 2-bromo5-fluoropyridine (0.456 g, 1.50 equiv), cesium carbonate (1.13 g, 2.01 equiv), and tetrakis(acetonitrile)copper(I) hexafluorophosphate (0.058 g, 0.090 equiv) in toluene (9 mL, 0.2 M) was heated to 100° C. in a Biotage Personal microwave for 10 minutes. The reaction mixture was filtered through Celite, and the Celite was washed with dichloromethane. The filtrate was concentrated and purified on 60 g silica gel using a gradient eluent consisting of 0-10% ethyl acetate/dichloromethane over 60 minutes to give the title compound as a white solid. 0.274 g, 41% yield. 1H NMR (400 MHz, CDCl3) δ ppm 1.46 (9H, s), 2.31 (2H, t, J=5.8 Hz), 2.45 (2H, t, J=5.4 Hz), 3.39 (2H, t, J=5.9 Hz), 3.49 (2H, t, J=5.9), 6.33 (1H, s), 6.85-6.98 (3H, m), 7.02 (1H, d, J=7.6 Hz), 7.33 (1H, t, J=7.8 Hz), 7.40-7.47 (1H, m), 8.03 (1H, d, J=3.1 Hz).

Workup

filtrationThe reaction mixture was filtered through Celite
washthe Celite was washed with dichloromethane
concentrationThe filtrate was concentrated
custompurified on 60 g silica gel using a gradient eluent

Sources & evidence

ORD record: ord-5cf34c7ac82643e1b4d0589f8fefd846
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08044052B2

Reaction notes

Loading…