3-Fluoroaniline → {4-[(3-Fluoro-phenylamino)-methyl]-2,6-dimethyl-phenyl}-carbamic acid ethyl ester

HRID 1820156Notes

Reaction equation

HRID 1820156 reaction equation
[CH2:1]([O:3][C:4](=[O:16])[NH:5][C:6]1[C:11]([CH3:12])=[CH:10][C:9]([CH:13]=O)=[CH:8][C:7]=1[CH3:15])[CH3:2].[F:17][C:18]1[CH:19]=[C:20]([CH:22]=[CH:23][CH:24]=1)[NH2:21].C([BH3-])#N.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.O.C(O)(=O)C>[CH2:1]([O:3][C:4](=[O:16])[NH:5][C:6]1[C:11]([CH3:12])=[CH:10][C:9]([CH2:13][NH:21][C:20]2[CH:22]=[CH:23][CH:24]=[C:18]([F:17])[CH:19]=2)=[CH:8][C:7]=1[CH3:15])[CH3:2]

Participants

8

Reactant 4

HCID 97423-FluoroanilineHCID 10340Sodium CarbonateHCID 5003444Sodium cyanoborohydride2×HCID 86229075(4-Formyl-2,6-dimethyl-phenyl)-carbamic acid ethyl ester

Product 1

HCID 11716670{4-[(3-Fluoro-phenylamino)-methyl]-2,6-dimethyl-phenyl}-carbamic acid ethyl esterYield 29%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
25 °C

Procedure

To (4-formyl-2,6-dimethyl-phenyl)-carbamic acid ethyl ester (230 mg) and 3-fluoroaniline (122 mg) dissolved in dry ethanol (25 mL) was added 3 Å molecular sieves (0.5 g) and the reaction mixture was refluxed for 16 hours under argon. Upon cooling to 25° C., sodium cyanoborohydride (320 mg) and acetic acid (3 mL) were added and stirred for 1 hour. A second batch of sodium cyanoborohydride (320 mg) was added and the mixture stirred for 1 additional hour. Saturated aqueous sodium carbonate (5 mL) was added and the mixture stirred for 1 hour, water (50 mL) was added and the mixture was extracted with ethyl acetate (3×25 mL). The combined organic phases were dried over magnesium sulfate, concentrated in vacuo and purified by flash chromatography to furnish 95 mg (29% yield) of the title compound as a white solid. LC-MS-TOF (m/z) 317 (MH+); tR=3.37, (UV, ELSD) 99%, 96%. 1H NMR (500 MHz, CDCl3): 1.31 (b, 3H), 2.25 (s, 6H), 4.20 (m, 5H), 5.98 (b, 1H), 6.30 (dt, 1H), 6.39 (m, 2H), 7.06 (s, 2H), 7.08 (q, 1H).

Workup

  1. additionwas added 3 Å molecular sieves (0.5 g)
  2. temperaturethe reaction mixture was refluxed for 16 hours under argon
  3. stirringthe mixture stirred for 1 additional hour
  4. stirringthe mixture stirred for 1 hour
  5. extractionthe mixture was extracted with ethyl acetate (3×25 mL)
  6. dry with materialThe combined organic phases were dried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. custompurified by flash chromatography

Sources & evidence

ORD record
ord-fc83ac6c2b53471eb82d840988fd76ad
Source dataset
uspto-grants-2009_10
Patent number
US07601870B2

Reaction notes

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