Hydrochloric Acid → 1-(2-Difluoromethoxy-4-nitro-phenyl)-4-isopropyl-piperazine

HRID 491622Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[O:11][CH:12]([F:14])[F:13].[CH3:15][CH:16]([N:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1)[CH3:17].C([O-])([O-])=O.[K+].[K+].Cl>CS(C)=O.O>[F:13][CH:12]([F:14])[O:11][C:3]1[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=1[N:21]1[CH2:22][CH2:23][N:18]([CH:16]([CH3:17])[CH3:15])[CH2:19][CH2:20]1

Participants

Conditions

Temperature: 120 °C

Procedure

1-Bromo-2-difluoromethoxy-4-nitro-benzene (Step A, 2.0 g, 7.5 mmol, 1.0 eq.) and N-(2-propyl)piperazine (0.85 mL, 9.7 mmol, 1.3 eq.) were dissolved in 20 mL of DMSO. K2CO3 (1.5 g, 11.2 mmol, 1.5 eq.) and Bu4N+Br− (240 mg, 0.75 mmol, 0.1 eq.) were added and the mixture was heated to 120° C. The mixture was stirred for 3 h and cooled to RT, poured into H2O (200 mL) and 6 N HCl (20 mL). The aqueous solution was washed with EtOAc, and alkalinized with 6 N NaOH then extracted with EtOAc. The combined organic layers were dried (MgSO4), filtered and concentrated. The crude material was further purified by column chromatography (0-100% EtOAc in hexanes) providing pure 1-(2-difluoromethoxy-4-nitro-phenyl)-4-isopropyl-piperazine.

Workup

temperaturecooled to RT
washThe aqueous solution was washed with EtOAc
extractionthen extracted with EtOAc
dry with materialThe combined organic layers were dried (MgSO4)
filtrationfiltered
concentrationconcentrated
customThe crude material was further purified by column chromatography (0-100% EtOAc in hexanes)

Sources & evidence

ORD record: ord-6cb5c834550344e6b84dc799bdddc55e
Source dataset: uspto-grants-2009_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07531553B2

Reaction notes

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