tert-Butyl piperazine-1-carboxylate → 3-(4-BOC-piperazino)-2-chloropyridine

HRID 604294Notes

Reaction equation

HRID 604294 reaction equation
[Cl:1][C:2]1[C:7](Br)=[CH:6][CH:5]=[CH:4][N:3]=1.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].CC(C)([O-])C.[Na+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>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].O>[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:7]2[C:2]([Cl:1])=[N:3][CH:4]=[CH:5][CH:6]=2)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

Participants

8

Reactant 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 6933243-Bromo-2-chloropyridineHCID 23676156Sodium t-butoxide

Product 1

HCID 593218363-(4-BOC-piperazino)-2-chloropyridineYield 51%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Stir 2-chloro-3-bromopyridine (5.00 g, 26.0 mmol) and piperazine-1-carboxylic acid t-butyl ester (3.73 g, 20.0 mmol) in dry toluene (200 mL) at room temperature under nitrogen. Add sodium t-butoxide (2.88 g, 30.0 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.366 g, 0.40 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.694 g, 1.20 mmol), degas reaction and heat to 100° C. (oil bath temperature) for 3 hr. Cool to room temperature, add 100 mL water, extract with 2×200 mL ethyl acetate. Concentrate organic layer in vacuo, purify (silica gel chromatography, eluting with 30:70 ethyl acetate:isohexane) and dry in a vacuum oven over night to give 4-(2-chloro-pyridin-3-yl)-piperazine-1-carboxylic acid t-butyl ester as a beige powder (3.01 g, 51%). MS (m/z): 298 (M+1).

Workup

  1. customreaction
  2. temperatureCool to room temperature
  3. extractionextract with 2×200 mL ethyl acetate
  4. customConcentrate organic layer in vacuo, purify
  5. wash(silica gel chromatography, eluting with 30:70 ethyl acetate:isohexane)
  6. customdry in a vacuum oven over night

Sources & evidence

ORD record
ord-69e606e628af4d36ba7bd3fac3e3eada
Source dataset
uspto-grants-2011_03
Patent number
US07910588B2

Reaction notes

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