Aniline → Dimethyl 2-anilinobenzene-1,4-dicarboxylate

HRID 970314

Reaction equation

HRID 970314 reaction equation
Br[C:2]1[CH:11]=[C:10]([C:12]([O:14][CH3:15])=[O:13])[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[NH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(OCC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH3:15][O:14][C:12](=[O:13])[C:10]1[CH:11]=[C:2]([NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:3]([C:4]([O:6][CH3:7])=[O:5])=[CH:8][CH:9]=1

Participants

8

Reactant 4

HCID 6115AnilineHCID 10796Cesium carbonateHCID 87741Dimethyl 2-bromoterephthalateHCID 634876Binap, (A+-)-

Product 1

HCID 16748523Dimethyl 2-anilinobenzene-1,4-dicarboxylate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of dimethyl bromoterephthalate (4.5 g, 16.0 mmol), aniline (2.2 mL, 24.0 mmol), (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (922 mg, 1.48 mmol), and toluene (50 mL) was added cesium carbonate (7.53 g, 23.1 mmol), followed by palladium(II) acetate (0.22 g, 1.0 mmol). The mixture was heated to 100° C. for 24 h. HPLC indicated that the reaction was complete. The reaction mixture was cooled to room temperature, diluted with diethyl ether and filtered under reduced pressure through a pad of Celite. The filtrate was concentrated under reduced pressure and purified by silica gel chromatography using a 1:10 mixture of EtOAc and hexane to give 4.58 (97%) of 1A as a bright yellow solid. HPLC retention time=3.74 min. (Condition A) and LC/MS M++1=286+. 1H-NMR (400 MHz, CDCl3): δ 9.50 (bs, 1H), 8.01 (d, J=8.30, 1H), 7.91 (d, J=1.50, 1H), 7.32-7.40 (m, 4H), 7.25 (m, 1H), 7.13 (m, 1H), 3.93 (s, 3H), 3.88 (s, 3H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered under reduced pressure through a pad of Celite
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. custompurified by silica gel chromatography
  5. additiona 1:10 mixture of EtOAc and hexane

Sources & evidence

ORD record
ord-0bf03931b142489ebaac81ba47c01ea0
Source dataset
uspto-grants-2007_12
Patent number
US07312209B2

Linked notes

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