p-Toluenesulfonic acid → HCID 178484003, compound

HRID 1382936Notes

Reaction equation

HRID 1382936 reaction equation
[CH2:1]([O:8][C:9]([N:11]([CH2:13][C@H:14]1[CH2:19][CH2:18][C@H:17]([C:20](O)=O)[CH2:16][CH2:15]1)[CH3:12])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.ClC(OCC(C)C)=O.[C:38]1([NH2:45])[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[NH2:44].C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCCC1.C1(C)C=CC=CC=1.O>[N:44]1[C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=2[NH:45][C:20]=1[C@H:17]1[CH2:18][CH2:19][C@H:14]([CH2:13][N:11]([CH3:12])[C:9](=[O:10])[O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:15][CH2:16]1

Participants

9

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 7243O-PhenylenediamineHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 178484086HCID 178484086, compound

Product 1

HCID 178484003HCID 178484003, compoundYield 33.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 13.6 g (0.044 mol) of trans-4-(N-benzyloxycarbonyl-N-methyl-aminomethyl)cyclohexanecarboxylic acid and 9.5 ml (0.068 mol) of triethylamine in 110 ml of tetrahydrofuran is treated at -15° within 30 minutes with 6.5 ml (0.049 mol) of isobutyl chloroformate. A solution of 5.8 g (0.053 mol) of o-phenylenediamine is then added dropwise at -15° within 45 minutes. The mixture is stirred at room temperature for 1 hour and left to stand for 20 hours. After concentration under reduced pressure the residue is partitioned between water and ethyl acetate and the organic phase is washed with a 5% solution of sodium hydrogen carbonate, then with a saturated aqueous solution of sodium chloride and finally with water. The solution, dried over magnesium sulphate, is evaporated and triturated with ether. The solid product obtained (9.3 g) is dissolved in 200 ml of toluene, 3 g of p-toluenesulphonic acid are added thereto and the mixture is heated to reflux for 4 hours with a water separator. The solution is cooled, washed with a 2N sodium carbonate solution and a saturated aqueous solution of sodium chloride, dried over magnesium sulphate and concentrated to dryness under reduced pressure. The solid residue is recrystallized from ethyl acetate. There are obtained 5.6 g of benzyl [[trans-4-(2-benzimidazolyl)cyclohexyl]methyl]methylcarbamate, m.p. 146°-148°, as a colourless crystalline powder. After chromatography on 250 g of silica gel with ethyl acetate/methylene chloride (9:1) as the elution agent the mother liquor gives a further 1.1 g of the same product, m.p. 146°-148°. Total yield: 6.7 g (40%).

Workup

  1. waitleft
  2. waitto stand for 20 hours
  3. concentrationAfter concentration under reduced pressure the residue
  4. customis partitioned between water and ethyl acetate
  5. washthe organic phase is washed with a 5% solution of sodium hydrogen carbonate
  6. dry with materialThe solution, dried over magnesium sulphate
  7. customis evaporated
  8. customtriturated with ether
  9. customThe solid product obtained (9.3 g)
  10. temperaturethe mixture is heated
  11. temperatureThe solution is cooled
  12. washwashed with a 2N sodium carbonate solution
  13. dry with materiala saturated aqueous solution of sodium chloride, dried over magnesium sulphate
  14. concentrationconcentrated to dryness under reduced pressure
  15. customThe solid residue is recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-aef97ad001084409bc87ca8f99808317
Source dataset
uspto-grants-1989_02
Patent number
US04808605

Reaction notes

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