Sodium Carbonate → 1-(3,5-Dichloro-4'-fluoro-biphenyl-4-ylmethyl)-3-(4-methoxy-cyclohexyl)-pyrrolidin-2-one

HRID 1670835Notes

Reaction equation

Br[C:2]1[CH:22]=[C:21]([Cl:23])[C:5]([CH2:6][N:7]2[CH2:11][CH2:10][CH:9]([CH:12]3[CH2:17][CH2:16][CH:15]([O:18][CH3:19])[CH2:14][CH2:13]3)[C:8]2=[O:20])=[C:4]([Cl:24])[CH:3]=1.[F:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.O.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:24][C:4]1[CH:3]=[C:2]([C:29]2[CH:30]=[CH:31][C:26]([F:25])=[CH:27][CH:28]=2)[CH:22]=[C:21]([Cl:23])[C:5]=1[CH2:6][N:7]1[CH2:11][CH2:10][CH:9]([CH:12]2[CH2:17][CH2:16][CH:15]([O:18][CH3:19])[CH2:14][CH2:13]2)[C:8]1=[O:20]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 1-(4-Bromo-2,6-dichloro-benzyl)-3-(4-methoxy-cyclohexyl)-pyrrolidin-2-one (0.4 g, 0.92 mmol) and 4-fluorophenylboronic acid (0.19 g, 1.38 mmol) in THF (15 mL) and water (5 mL) and sodium carbonate (0.29, 0.75 g) is purged with N2. Treat the reaction with Pd(PPh3)4 (0.05 g, 0.046 mmol) and heat to 80° C. for 2 hour under N2. Cool the reaction, dilute with ethyl acetate, and wash with HCl (1N) and water. Dry the organic layer (Na2SO4), remove the solvent in vacuo to afford crude product, and purify with a 35% ethyl acetate in hexanes to afford 0.45 g of the titled product. MS (m/z): 451 (M+).

Workup

customis purged with N2
additionTreat
temperatureCool
customthe reaction
washwash with HCl (1N) and water
dry with materialDry the organic layer (Na2SO4)
customremove the solvent in vacuo
customto afford crude product
custompurify with a 35% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-975f527875ca4ec8bd91b2c1d6dc0e15
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07994176B2

Reaction notes

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