Hydrochloric Acid → 4-(4-(Tert-butoxycarbonyl)piperazin-1-yl)-3-methylbenzoic acid

HRID 44322Notes

Reaction equation

[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)=[C:5]([CH3:22])[CH:4]=1)#N.[OH-:23].[Na+].Cl.[OH2:26]>CCO>[C:18]([O:17][C:15]([N:12]1[CH2:13][CH2:14][N:9]([C:6]2[CH:7]=[CH:8][C:3]([C:1]([OH:26])=[O:23])=[CH:4][C:5]=2[CH3:22])[CH2:10][CH2:11]1)=[O:16])([CH3:21])([CH3:20])[CH3:19]

Participants

Conditions

Temperature: 90 °C

Procedure

To a suspension of tert-butyl 4-(4-cyano-2-methylphenyl)piperazine-1-carboxylate (3.685 g, 12.23 mmol) in EtOH (Volume: 50 mL) and Water (Volume: 10 mL) was added Sodium hydroxide solution (8.48 mL, 162 mmol) at 23° C. Rinsed sodium hydroxide forward with Water (Volume: 2.5 mL). The reaction was stirred at 90° C. for 10 hr. The reaction mixture was cooled to 23° C., neutralized with 3N HCl (52 mL), filtered, rinsed with H2O (3×10 mL), and the resulting solid was dried in vacuo to provide 4-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-methylbenzoic acid (3.588 g, 11.20 mmol, 92% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.42 (s, 9 H) 2.29 (s, 3 H) 2.81-2.90 (m, 4 H) 3.42-3.53 (m, 4 H) 7.05 (d, J=8.08 Hz, 1 H) 7.70-7.77 (m, 2 H) 12.61 (br. s., 1 H). ESI-MS: m/z 321.2 (M+H)+. mp=174.7-178.6° C.

Workup

temperatureThe reaction mixture was cooled to 23° C.
filtrationfiltered
washrinsed with H2O (3×10 mL)
customthe resulting solid was dried in vacuo

Sources & evidence

ORD record: ord-eab72efd3e7f4175a888e918598eacc9
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08541417B2

Reaction notes

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