Citric Acid → 3-(1-Cyano-1-methylethyl)-N-(4-methyl-3-nitro-phenyl)benzamide

HRID 1184814Notes

Reaction equation

HRID 1184814 reaction equation
[C:1]([C:3]([C:6]1[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=1)[C:9]([OH:11])=O)([CH3:5])[CH3:4])#[N:2].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:46][C:47]1[CH:53]=[CH:52][C:50]([NH2:51])=[CH:49][C:48]=1[N+:54]([O-:56])=[O:55].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C>[C:1]([C:3]([C:6]1[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=1)[C:9]([NH:51][C:50]1[CH:52]=[CH:53][C:47]([CH3:46])=[C:48]([N+:54]([O-:56])=[O:55])[CH:49]=1)=[O:11])([CH3:4])[CH3:5])#[N:2]

Participants

7

Reactant 5

HCID 311Citric AcidHCID 83904-Methyl-3-nitroanilineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 571495383-(2-Cyanopropan-2-yl)benzoic acid

Product 1

HCID 671255393-(1-Cyano-1-methylethyl)-N-(4-methyl-3-nitro-phenyl)benzamideYield 63.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-(2-cyanopropan-2-yl)benzoic acid 3 (25 g, 132 mmol), TBTU (63 g, 98 mmol), DIPEA (396 mmol, 65.4 mL) and 4-methyl-3-nitroaniline (20.1 g, 132 mmol) were dissolved in DMF (500 mL) and stirred for 72 h. The reaction mixture was poured into citric acid solution (3%) and extracted twice with EtOAc. The combined organic layers were washed with water (5×), brine (2×), dried, and evaporated. Purification by chromatography (CH2Cl2) gave 3-(2-cyanopropan-2-yl)-N-(4-methyl-3-nitrophenyl)benzamide 4 (27 g, 63%). 1H-NMR (400 MHz, CDCl3) 1.78 (s, 6H), 2.60 (s, 3H), (d, J=8.5 Hz, 1H), 7.55 (t, J=7.6 Hz, 1H), 7.73 (m, 1H), 7.80 (m, 1H), 7.90 (m, 1H), 7.99 (m, 1H), 8.06 (br s, 1H), 8.28 (m, 1H).

Workup

  1. extractionextracted twice with EtOAc
  2. washThe combined organic layers were washed with water (5×), brine (2×)
  3. customdried
  4. customevaporated
  5. customPurification by chromatography (CH2Cl2)

Sources & evidence

ORD record
ord-73586443a3854c9b892b6fe6d77126ac
Source dataset
uspto-grants-2014_03
Patent number
US08669256B2

Reaction notes

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