Sodium Iodide → tert-Butyl piperazine-1-carboxylate

HRID 565200Notes

Reaction equation

N1CCC(CNC(C2C3OCCOC=3C=CC=2)=O)CC1.[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][N:31](S(CCCCl)(=O)=O)[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].[I-].[Na+].C(N(CC)CC)C>CN(C)C=O>[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:22])[CH3:23]

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 2,3-dihydrobenzo[1,4]dioxine-5-carboxylic acid(piperidin-4-ylmethyl)amide (28.6 g, 104 mmol), 4-(3-chloropropane-1-sulfonyl)piperazine-1-carboxylic acid tert-butyl ester (33.9 g, 104 mmol), sodium iodide (7.8 g, 52 mmol), and triethylamine (29 mL, 209 mmol) in N,N-dimethylformamide (70 mL) was stirred at 90° C. for 4 hours. The cooled reaction mixture was partitioned between ethyl acetate and water. The ethyl acetate layer was washed with water (three times) and brine, dried (Na2SO4) and the solvents evaporated in vacuo. The crude product was purified by silica gel chromatography (5% methanol-dichloromethane) and crystallization from ethyl acetate-hexane to give 4-[3-(4-{[2,3-dihydrobenzo[1,4]dioxin-5-carbonyl)amino]-methyl}piperidin-1-yl)propane-1-sulfonyl]piperazine-1-carboxylic acid tert-butyl ester (37.5 g, 64%); m.p. 130-132° C. Analysis for C27H43N4O7 S: Calcd.: C, 57.12; H, 7.63; N, 9.87. Found: C, 57.01; H, 7.40; N, 9.94.

Workup

customThe cooled reaction mixture
customwas partitioned between ethyl acetate and water
washThe ethyl acetate layer was washed with water (three times) and brine
dry with materialdried (Na2SO4)
customthe solvents evaporated in vacuo
customThe crude product was purified by silica gel chromatography (5% methanol-dichloromethane) and crystallization from ethyl acetate-hexane

Sources & evidence

ORD record: ord-022893ad69904bbaa3719462a07a4ca1
Source dataset: uspto-grants-2001_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06172062B2

Reaction notes

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