tert-Butyl piperazine-1-carboxylate → HCID 66691662, compound

HRID 1808880Notes

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.Br[C:15]1[CH:16]=[CH:17][C:18]([CH3:29])=[C:19]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH:20]=1.CCOC(C)=O.C(Cl)Cl>C1(C)C=CC=CC=1.C(O[Pd]OC(=O)C)(=O)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>[C:24]([O:23][C:22]([NH:21][C:19]1[CH:20]=[C:15]([N:4]2[CH2:5][CH2:6][N:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:2][CH2:3]2)[CH:16]=[CH:17][C:18]=1[CH3:29])=[O:28])([CH3:27])([CH3:26])[CH3:25]

Participants

Conditions

Temperature: 105 °C

Procedure

A mixture of tert-butyl piperazine-1-carboxylate (5.47 g, 29.4 mmol), tert-butyl 5-bromo-2-methylphenylcarbamate (2.8 g, 9.78 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.233 g, 0.489 mmol), diacetoxypalladium (0.066 g, 0.294 mmol), and Reactant 5 (9.56 g, 29.4 mmol) (Cs2CO3) in Toluene (45 mL) was heated at 100-110° C. for 2 days. After the solvent was removed, the residue was dissolved in ethyl acetate and washed with water. After the EtOAc was removed, the residue was purified by column with DCM, then EtOAc/DCM (2%) to give tert-butyl 4-(3-(tert-butoxycarbonylamino)-4-methylphenyl)piperazine-1-carboxylate (2.5 g, 6.39 mmol, 65.3% yield, white solid). 1H-NMR (CDCl3, 500 MHz): δ 7.57 (1H, s), 7.00 (1H, d, J=8.55 Hz), 6.55 (1H, d, J=8.24 Hz), 6.31 (1H, s), 3.56 (4H, m), 3.09 (4H, m), 2.15 (3H, s), 1.52 (9H, s), 1.48 (9H, s).

Workup

customAfter the solvent was removed
dissolutionthe residue was dissolved in ethyl acetate
washwashed with water
customAfter the EtOAc was removed
customthe residue was purified by column with DCM

Sources & evidence

ORD record: ord-e9e088eed382475a90bbce1cd7b2af62
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08362004B2

Reaction notes

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