Sodium Carbonate → 1-(4-chloro-1,1'-biphenyl-3-yl)-N-(cyanomethyl)piperidine-2-carboxamide

HRID 1744164Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:20])=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]2[C:14]([NH:16][CH2:17][C:18]#[N:19])=[O:15])[CH:7]=1.[C:21]1(B(O)O)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:20][C:5]1[CH:4]=[CH:3][C:2]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:7][C:6]=1[N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[C:14]([NH:16][CH2:17][C:18]#[N:19])=[O:15]

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 1-(5-bromo-2-chlorophenyl)-N-(cyanomethyl)piperidine-2-carboxamide (125 mg, 0.35 mmol), phenylboronic acid (64 mg, 0.53 mmol), PdCl2(dppf) (29 mg, 0.035 mmol) and 2 N Na2CO3 (0.5 mL, 1.1 mmol) in DMF (3.5 mL) was degassed and then heated to 110° C. for 4 h. The mixture was cooled and partitioned between water and ethyl acetate. The aqueous layer was extracted with ethyl acetate (3×) and the combined organic layers were dried over Na2SO4 and concentrated. Purification by flash chromatography (50% Et2O/hexanes) afforded 1-(4-chloro-1,1′-biphenyl-3-yl)-N-(cyanomethyl)piperidine-2-carboxamide.

Workup

customwas degassed
temperatureThe mixture was cooled
custompartitioned between water and ethyl acetate
extractionThe aqueous layer was extracted with ethyl acetate (3×)
dry with materialthe combined organic layers were dried over Na2SO4
concentrationconcentrated
customPurification by flash chromatography (50% Et2O/hexanes)

Sources & evidence

ORD record: ord-0e35022499b1405f9e7fde2588006015
Source dataset: uspto-grants-2006_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07012075B2

Reaction notes

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