Water → Tert-butyl 4-[4-(5-amino-3-methylisoxazol-4-yl)phenyl]piperazine-1-carboxylate

HRID 1744136Notes

Reaction equation

Br[C:2]1[C:3]([CH3:8])=[N:4][O:5][C:6]=1[NH2:7].[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:22]2[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=2)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].C(=O)([O-])[O-].[Na+].[Na+].O>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:7][C:6]1[O:5][N:4]=[C:3]([CH3:8])[C:2]=1[C:25]1[CH:24]=[CH:23][C:22]([N:19]2[CH2:18][CH2:17][N:16]([C:14]([O:13][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:15])[CH2:21][CH2:20]2)=[CH:27][CH:26]=1

Participants

Conditions

Temperature: 95 °C

Procedure

To 4-bromo-3-methylisoxazol-5-amine (2.63 g, 14.85 mmol), 4-[4-(tert-butoxycarbonyl)-1-piperazinyl]phenylboronic acid (5.7 g, 18.57 mmol, prepared as described in Example 1) and catalyst PdCl2(dppf) (365 mg, 0.45 mmol) in DMF (100 mL) under dry nitrogen was added aqueous sodium carbonate (2.0 M, 18.6 mL, 37 mmol). The reaction was heated to 95° C. for 1 hour and an additional aliquot of PdCl2(dppf) (365 mg, 0.45 mmol) was added and the reaction mixture was heated overnight. Water was added and the product extracted with ether (2×), dried over Na2SO4, concentrated in vacuo, and purified by flash chromatography over silica gel (EtOAc/Hex, 4/6, then 1/1) to afford tert-butyl 4-[4-(5-amino-3-methylisoxazol-4-yl)phenyl]piperazine-1-carboxylate.

Workup

temperaturethe reaction mixture was heated overnight
extractionthe product extracted with ether (2×)
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
custompurified by flash chromatography over silica gel (EtOAc/Hex, 4/6

Sources & evidence

ORD record: ord-c1605f9545074d56836b9af62f469499
Source dataset: uspto-grants-2006_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07012075B2

Reaction notes

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