tert-Butyl piperazine-1-carboxylate → Tert-butyl 4-(5-(benzyloxy)pyridin-2-YL)piperazine-1-carboxylate

HRID 103

Reaction equation

HRID 103 reaction equation
CC(C)(C)OC(=O)N1CCNCC1.Clc1ccc(OCc2ccccc2)cn1>CC(C)(C)[O-].Cc1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.[Na+].[Pd].c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1>CC(C)(C)OC(=O)N1CCN(c2ccc(OCc3ccccc3)cn2)CC1

Participants

7

Reactant 2

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 100137175-(Benzyloxy)-2-chloropyridine

Product 1

HCID 22221503Tert-butyl 4-(5-(benzyloxy)pyridin-2-YL)piperazine-1-carboxylateYield 68.75%

Reagents, catalysts & solvents 4

HCID 23676156Sodium t-butoxideReagentHCID 634876Binap, (A+-)-CatalystHCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

BIS(DIBENZYLIDENEACETONE)PALLADIUM (0.055 g, 0.10 mmol) was added to tert- butyl piperazine-1-carboxylate (1.952 g, 10.48 mmol), 5-(benzyloxy)-2-chloropyridine (2.093 g, 9.53 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.059 g, 0.10 mmol) and sodium 2-methylpropan-2-olate (1.282 g, 13.34 mmol) in toluene (30 mL) at 20ºC under nitrogen. The resulting solution was stirred at 80 °C for 16 hours then cooled to room temperature. The reaction mixture was filtered through celite, filtrate partitioned between ethyl acetate (100 mL) and water (100 mL). The organic phase was dried (Na2SO4), filtered and evaporated to give a brown gum. The crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford tert-butyl 4-(5-(benzyloxy)pyridin-2-yl)piperazine-1-carboxylate (2.420 g, 68.7 %) as a yellow solid.

Sources & evidence

ORD record
ord-8fcffc24262340ad8745959198669390
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Linked notes

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