4-Aminobiphenyl → N-biphenyl-4-yl-malonamic acid ethyl ester

HRID 1093665Notes

Reaction equation

[C:1]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:2][C:3]([O-:5])=O.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[C:32]1([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH:37]=[CH:36][C:35]([NH2:38])=[CH:34][CH:33]=1>CN(C=O)C.CN(C1C=CN=CC=1)C.O>[CH2:8]([O:7][C:1](=[O:6])[CH2:2][C:3]([NH:38][C:35]1[CH:34]=[CH:33][C:32]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)=[CH:37][CH:36]=1)=[O:5])[CH3:9]

Participants

Conditions

Temperature: 10 °C

Procedure

To a stirred solution of monoethyl malonate (0.86 g, 0.00649 mole) in DMF (20 mL) was added HOBt (0.795 g, 0.0059 mole) and DMAP (0.790 g, 0.00649 mole). The mixture was cooled to 10° C. and EDCI.HCl (1.7 g, 0.008 mole) followed by biphenyl-4-ylamine (1.0 g, 0.0059 mole) were added and the resulting mixture was stirred at the ambient temperature for overnight. The reaction mixture was then diluted with cold water and the resulting precipitate was isolated by filtration and dried to afford 1.76 g (94%) of N-biphenyl-4-yl-malonamic acid ethyl ester. To a solution of N-biphenyl-4-yl-malonamic acid ethyl ester (1.7 g, 0.0060 mole) in a mixture of methanol (5 mL), THF (10 mL) and H2O (10 mL) was added LiOH.H2O (0.5 g, 0.012 mole). The reaction mixture was stirred for 2 hours at ambient temperature. The mixture was then concentrated and the residue was diluted with water acidified with conc. HCl. The resulting precipitate was isolated by filtration and dried to afford 1.5 g (98%) of N-biphenyl-4-yl-malonamic acid. LC-MS purity: 95.4%, 1H NMR (DMSO-d6): δ 10.3 (s, 1H), 7.7 (m, 6H), 7.4 (t, 2H), 7.32 (t, 1H).

Workup

additionwere added
customthe resulting precipitate was isolated by filtration
customdried

Sources & evidence

ORD record: ord-296a32e459a44cd082b04b6bc275f2fc
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08129376B2

Reaction notes

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