4-Cyclohexylbenzenamine → HCID 46841138, compound

HRID 1846323Notes

Reaction equation

HRID 1846323 reaction equation
[NH2:1][C:2]1[CH:22]=[CH:21][CH:20]=[CH:19][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)=[CH:9][CH:8]=1)=[O:5].C1(C2C=CC(N)=CC=2)CCCCC1.[Si]([O:43][CH2:44][CH2:45][O:46][C:47]1[C:54]([CH3:55])=[CH:53][C:50]([CH:51]=O)=[CH:49][C:48]=1[CH3:56])(C(C)(C)C)(C)C>C(O)C>[CH:13]1([C:10]2[CH:11]=[CH:12][C:7]([N:6]3[C:4](=[O:5])[C:3]4[C:2](=[CH:22][CH:21]=[CH:20][CH:19]=4)[N:1]=[C:51]3[C:50]3[CH:53]=[C:54]([CH3:55])[C:47]([O:46][CH2:45][CH2:44][OH:43])=[C:48]([CH3:56])[CH:49]=3)=[CH:8][CH:9]=2)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

5

Reactant 3

HCID 807644-CyclohexylbenzenamineHCID 866219154-(2-(Tert-butyldimethylsilyloxy)ethoxy)-3,5-dimethylbenzaldehydeHCID 86659808HCID 86659808, compound2×

Product 1

HCID 46841138HCID 46841138, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Following the method described for Example 21, 2-amino-N-(4-cyclohexylphenyl)benzamide was made from 4-cyclohexylaniline in 70% yield and isolated as a white solid. 2-Amino-N-(4-cyclohexylphenyl)-benzamide (4.58 mmol), 4-(2-(tert-butyldimethylsilyloxy)ethoxy)-3,5-dimethylbenzaldehyde (1.41 g, 4.58 mmol), anhydrous CuCl2 (1.84 g, 13.74 mmol) were combined in anhydrous ethanol (100 mL) and heated at reflux for 7 hours. The mixture was concentrated, diluted with ethyl acetate (300 mL), washed with water (100 mL) and then brine (150 mL), dried over Na2SO4, filtered, and concentrated. Purification by flash chromatography on silica gel, eluting with 50% ethyl acetate/hexanes to 100% ethyl acetate, afforded the title compound in 55% yield, as a white solid. 1H-NMR (300 MHz, DMSO-6): δ 8.18 (d, J=7.5 Hz, 1H), 7.86-7.92 (m, 1H), 7.74 (d, J=8.1 Hz, 1H), 7.55-7.60 (m, 1H), 7.15-7.17 (m, 4H), 6.96 (s, 2H), 4.84 (t, J=5.3 Hz, 1H), 3.62-3.36 (m, 4H), 2.48-2.50 (m, 1H), 2.06 (s, 6H), 1.67-1.78 (m, 5H), 1.32-1.39 (m, 5H). MS (ESI) m/z: 469 (M+H)+.

Workup

  1. customisolated as a white solid
  2. temperatureheated
  3. temperatureat reflux for 7 hours
  4. concentrationThe mixture was concentrated
  5. additiondiluted with ethyl acetate (300 mL)
  6. washwashed with water (100 mL)
  7. dry with materialbrine (150 mL), dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by flash chromatography on silica gel
  11. washeluting with 50% ethyl acetate/hexanes to 100% ethyl acetate

Sources & evidence

ORD record
ord-f805f71eb77a491c96e06a3cbaf5dd2d
Source dataset
uspto-grants-2015_02
Patent number
US08952021B2

Reaction notes

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