Hydrochloric Acid → HCID 86618626, compound

HRID 1436474Notes

Reaction equation

HRID 1436474 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][C@H:5]([C:8]([OH:10])=[O:9])[CH2:4][CH2:3]1.C(N(CC)CC)C.C([N:26]=[C:27]=[S:28])(=O)C1C=CC=CC=1.[OH-].[Li+].Br[CH2:32][C:33]([C:35]1[CH:40]=[CH:39][C:38]([Br:41])=[CH:37][CH:36]=1)=O.Cl>C1COCC1.O>[Br:41][C:38]1[CH:39]=[CH:40][C:35]([C:33]2[N:26]=[C:27]([NH:1][CH:2]3[CH2:7][CH2:6][CH:5]([C:8]([OH:10])=[O:9])[CH2:4][CH2:3]3)[S:28][CH:32]=2)=[CH:36][CH:37]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 74544-Bromophenacyl bromideHCID 8471TriethylamineHCID 68284Benzoyl isothiocyanateHCID 178511566HCID 178511566, compound

Product 1

HCID 86618626HCID 86618626, compoundYield 10%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

cis-4-Amino-1-cyclohexanecarboxylic acid (1.43 g, 10 mmol) was suspended in THF (30 mL) and triethylamine (1.31 mL, 9.5 mmol) was added, followed by benzoylisothio-cyanate (1.36 mL, 10 mmol). The mixture was heated to reflux for 2 h, cooled, and stirred for 48 h. Lithium hydroxide (1N aqueous solution, 20 mL, 20 mmol) was added, the mixture was heated to reflux for 1 h, and the mixture was then cooled to 25° C. 2-Bromo-1-(4-bromo-phenyl)-ethanone (2.78 g, 10 mmol) was added, the mixture was heated to reflux for 1 h, and the mixture was then cooled to 25° C. The mixture was diluted with water, acidified with 2N HCl, and extracted with ethyl acetate. The organics were combined and washed with brine, dried over MgSO4, and concentrated. Flashing with 25% acetone in hexane with 0.5% acetic acid gave the intermediate 4-[4-(4-bromophenyl)-thiazol-2-ylamino]-cyclohexanecarboxylic acid (0.38 g).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 2 h
  3. temperaturecooled
  4. temperaturethe mixture was heated
  5. temperatureto reflux for 1 h
  6. temperaturethe mixture was heated
  7. temperatureto reflux for 1 h
  8. temperaturethe mixture was then cooled to 25° C
  9. extractionextracted with ethyl acetate
  10. washwashed with brine
  11. dry with materialdried over MgSO4
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-dfcd63c9ed7241d28eb888a7668824e1
Source dataset
uspto-grants-2009_11
Patent number
US07618990B2

Reaction notes

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