1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2,3,5,6-tetrafluoro-4-methyl-N-(2-methylcyclohexyl)benzamide

HRID 1644114Notes

Reaction equation

[F:1][C:2]1[C:7]([F:8])=[C:6]([C:9]([OH:11])=O)[C:5]([F:12])=[C:4]([F:13])[C:3]=1[CH3:14].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[CH3:36][CH:37]1[CH2:42][CH2:41][CH2:40][CH2:39][CH:38]1[NH2:43]>C(Cl)Cl.CN(C=O)C>[F:12][C:5]1[C:4]([F:13])=[C:3]([CH3:14])[C:2]([F:1])=[C:7]([F:8])[C:6]=1[C:9]([NH:43][CH:38]1[CH2:39][CH2:40][CH2:41][CH2:42][CH:37]1[CH3:36])=[O:11]

Participants

Conditions

Temperature: 0 °C

Procedure

2,3,5,6-tetrafluoro-p-toluic acid (4.00 g, 19.22 mmol), HOBt (5.19 g, 38.44 mmol) and EDCI (4.42 g 23.06 mmol) were mixed in 200 ml of anhydrous DCM and 30 ml of anhydrous DMF. The mixture was cooled to 0° C. and allowed to stir under Ar for 15 minutes. To the mixture was added 2-methylcyclohexanamine (3.05 mL, 23.06 mmol) and the reaction mixture was allowed to slowly warm to ambient temperature and stirred overnight. The reaction mixture was diluted with DCM, washed with 1N HCl, water, aqueous NaHCO3, water and brine, drying over MgSO4, filtration and removal of solvent in vacuo, afforded the crude product as a pale yellow solid Recrystallization (EtOH/H2O) and drying in vacuo gave 5.23 g of the title compound as a white solid (mixture of 2 diasteromers, 90%). 1H NMR (CDCl3) δ 0.95, 1.01 (d, J=7.0, 6.6 Hz, 3H) 1.1-2.1 (m, 9H), 2.29 (m, 3H), 3.70, 4.29 (m, 1H), 5.65, 5.92 (m, 1H). MS (304.1, M+H). m.p. 202-204° C.

Workup

temperatureto slowly warm to ambient temperature
stirringstirred overnight
washwashed with 1N HCl, water, aqueous NaHCO3, water and brine
dry with materialdrying over MgSO4, filtration and removal of solvent in vacuo
customafforded
customthe crude product as a pale yellow solid Recrystallization (EtOH/H2O)
customdrying in vacuo

Sources & evidence

ORD record: ord-acfbd195e6f640699c69e36d46ce895c
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08124121B2

Reaction notes

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