Nitrogen → 1-(3,5-Dichloro-4'-fluoro-biphenyl-4-ylmethyl)-3-piperidin-1-yl-pyrrolidin-2-one

HRID 1670842Notes

Reaction equation

Br[C:2]1[CH:20]=[C:19]([Cl:21])[C:5]([CH2:6][N:7]2[CH2:11][CH2:10][CH:9]([N:12]3[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]3)[C:8]2=[O:18])=[C:4]([Cl:22])[CH:3]=1.[F:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.N#N>C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:22][C:4]1[CH:3]=[C:2]([C:27]2[CH:28]=[CH:29][C:24]([F:23])=[CH:25][CH:26]=2)[CH:20]=[C:19]([Cl:21])[C:5]=1[CH2:6][N:7]1[CH2:11][CH2:10][CH:9]([N:12]2[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)[C:8]1=[O:18]

Participants

Conditions

Temperature: 90 °C

Procedure

Purge a mixture of 1-(4-bromo-2,6-dichloro-benzyl)-3-piperidin-1-yl-pyrrolidin-2-one (0.150 g, 0.37 mmol) and 4-fluorophenylboronic acid (0.150 g, 1.07 mmol) in toluene (7 mL) and 2M sodium carbonate (1.3 mL) with N2. Treat the reaction with Pd(PPh3)4 (0.043 g, 0.037 mmol) and heat to 90° C. for 4 hours under N2. Cool the reaction, dilute with ethyl acetate, and wash with and water. Dry the organic layer (Na2SO4), remove the solvent in vacuo to afford crude product, and purify with a 0 to 10% methanol in CH2Cl2 gradient to afford 0.050 g (32%) of the titled product. Rf=0.46 (9/1 CH2Cl2/methanol). ES MS (m/z): 421 (M+).

Workup

customPurge
additionTreat
temperatureCool
customthe reaction
washwash with and water
dry with materialDry the organic layer (Na2SO4)
customremove the solvent in vacuo
customto afford crude product
custompurify with a 0 to 10% methanol in CH2Cl2 gradient

Sources & evidence

ORD record: ord-b9e46ba1905d42c88ba5925495ea42c4
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07994176B2

Reaction notes

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