Triethylamine → 3-{3-[(3,5-Bis-trifluoromethyl-benzoyl)-methyl-amino]-pyridin-4-yl}-4-methyl-benzoic acid methyl ester

HRID 878068Notes

Reaction equation

Cl[C:2]1[CH:3]=[CH:4][C:5]([CH3:32])=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:14]([CH3:31])[C:15](=[O:30])[C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([C:26]([F:29])([F:28])[F:27])[CH:17]=2)[CH:7]=1.CCN(CC)CC.C[CH2:41][O:42][C:43](C)=[O:44]>CO.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].C(Cl)Cl>[CH3:41][O:42][C:43](=[O:44])[C:2]1[CH:3]=[CH:4][C:5]([CH3:32])=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:14]([C:15](=[O:30])[C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:23])[F:24])[CH:19]=[C:18]([C:26]([F:29])([F:27])[F:28])[CH:17]=2)[CH3:31])[CH:7]=1

Participants

Conditions

Temperature: 150 °C

Procedure

To a solution of N-[4-(5-chloro-2-methyl-phenyl)-pyridin-3-yl]-N-methyl-3,5-bis-trifluoromethyl-benzamide (160 mg, 338 μmol, example 82) in MeOH (1.2 mL) and EtOAc (1.2 mL) was added PdCl2(dppf)-CH2Cl2 complex (31.8 mg, 38.9 μmol, CAS RN 851232-71-8) and NEt3 (51.4 mg, 70.7 μL, 508 μmol). The reaction mixture was stirred at 150° C. at 70 bar under CO atmosphere for 24 hours. The reaction mixture was treated with silica gel and directly purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). Light yellow oil (39 mg, 23%). MS (ESI): m/z=497.129 [M+H]+.

Workup

additionThe reaction mixture was treated with silica gel
customdirectly purified by silica gel chromatography
washeluting with a gradient of n-heptane:EtOAc (100:0 to 0:100)

Sources & evidence

ORD record: ord-fd8a84e3ba4e47db8b404ad517bc6695
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08987307B2

Reaction notes

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