3,5-Dibromopyridine → Tert-butyl 4-(5-bromopyridin-3-yl)piperazine-1-carboxylate

HRID 331027Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.[N:9]1([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[Br:8][C:6]1[CH:7]=[C:2]([N:12]2[CH2:11][CH2:10][N:9]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:14][CH2:13]2)[CH:3]=[N:4][CH:5]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a suspension of 3,5-dibromopyridine (2 g, 8.44 mmol), 1,1-dimethylethyl 1-piperazinecarboxylate (1.572 g, 8.44 mmol), BINAP (0.210 g, 0.338 mmol) and sodium tert-butoxide (1.136 g, 11.82 mmol) in Toluene (50 mL) at RT, was added Pd2dba3 (0.42 g, 0.459 mmol). The reaction mixture was heated at 100° C. for 3 hours and was cooled to RT, followed by filtration through a short pad of celite (washed with ethyl acetate). The filtrate was concentrated in vacuo to give a residue, which was purified on silica gel, eluting with a gradient of 0-20% ethyl acetate in cyclohexane, to give the title compound (1.8 g). LCMS (A): m/z (M+H)+ 342/344, C14H20BrN3O2 requires 341/343 (acidic).

Workup

temperaturewas cooled to RT
filtrationfollowed by filtration through a short pad of celite (washed with ethyl acetate)
concentrationThe filtrate was concentrated in vacuo
customto give a residue, which
customwas purified on silica gel
washeluting with a gradient of 0-20% ethyl acetate in cyclohexane

Sources & evidence

ORD record: ord-a7cf4838b73948d6851520eb30244e93
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08877742B2

Reaction notes

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