Triethylamine → tert-Butyl 4-(2-chloronicotinoyl)piperazine-1-carboxylate

HRID 79209Notes

Reaction equation

HRID 79209 reaction equation
[N:1]1([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.C(N(CC)CC)C.Cl[C:22]1[N:27]=[CH:26][C:25]([C:28](Cl)=[O:29])=[CH:24][CH:23]=1.CO.C(Cl)[Cl:34]>CN(C)C1C=CN=CC=1.C(Cl)Cl>[Cl:34][C:26]1[N:27]=[CH:22][CH:23]=[CH:24][C:25]=1[C:28]([N:4]1[CH2:5][CH2:6][N:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:2][CH2:3]1)=[O:29]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 27821656-Chloronicotinoyl ChlorideHCID 21226129Dichloromethane methanol

Product 1

HCID 4321619tert-Butyl 4-(2-chloronicotinoyl)piperazine-1-carboxylateYield 89%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred ice-cooled solution of tert-butyl 1-piperazinecarboxylate (2.2 g, 12 mmol), triethylamine (3.2 mL, 23 mmol), and 4-dimethylaminopyridine (0.014 g, 0.11 mmol) in DCM (15 mL) was added 6-chloropyridine-3-carbonyl chloride (2.0 g, 11 mmol) in one portion. The resulting mixture was stirred at 0° C. and gradually warmed up to ambient temperature for 20 h. Upon workup, the mixture was subjected to combi-flash column chromatography (methanol/DCM) to give compound 351 (3.3 g, 89% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.46 (1 H, d, J=2.0 Hz), 7.74 (1 H, dd, J=8.2, 2.3 Hz), 7.42 (1 H, dd, J=8.2, 0.8 Hz), 3.20-4.02 (8 H, m), 1.48 (9 H, s). LCMS-ESI (POS), M/Z, M+1: Found 326.0.

Workup

  1. temperaturegradually warmed up to ambient temperature for 20 h

Sources & evidence

ORD record
ord-af2914b2e197410da17757f6a76e2c5a
Source dataset
uspto-grants-2014_09
Patent number
US08841312B2

Reaction notes

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