p-Bromochlorobenzene → 4-(4-Chloro-phenyl)-3-methyl-piperazine-1-carboxylic acid tert-butyl ester

HRID 917151Notes

Reaction equation

HRID 917151 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH:10]([CH3:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=1.CC(C)([O-])C.[Na+].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>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)[CH:10]([CH3:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 4

HCID 7806p-BromochlorobenzeneHCID 634876Binap, (A+-)-HCID 2756810tert-Butyl 3-methylpiperazine-1-carboxylateHCID 23676156Sodium t-butoxide

Product 1

HCID 667579574-(4-Chloro-phenyl)-3-methyl-piperazine-1-carboxylic acid tert-butyl esterYield 68%

Conditions

Temperature
120 °C

Procedure

To a solution of 3-Methyl-piperazine-1-carboxylic acid tert-butyl ester (1.0 g, 5 mmol) and 4-bromochlorobenzene (0.77 g, 4 mmol) was added sodium tert-butoxide (0.96 g, 10 mmol), palladium(1H) dibenzylideneacetone (Pd2DBA3, 0.09 g, 0.1 mmol), and BINAP (0.19 g, 0.3 mmol). The suspension was stirred at 120° C. for 10 hours. The reaction was filtered through celite and evaporated in vacuo. The residue was purified by silica gel chromatography (hexane→ethyl acetate) to yield 0.84 g (68%) of the title compound. 1H-NMR (CDCl3): δ 1.00 (3H, m), 1.74 (9H, s), 3.10 (3H, m), 3.30 (1H, m), 3.80 (2H, m), 4.10 (1H, brs), 6.85 (2H, d), 7.20 (2H, d).

Workup

  1. filtrationThe reaction was filtered through celite
  2. customevaporated in vacuo
  3. customThe residue was purified by silica gel chromatography (hexane→ethyl acetate)

Sources & evidence

ORD record
ord-dce03c68994a499db1af37615e60d769
Source dataset
uspto-grants-2007_09
Patent number
US07271176B2

Reaction notes

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