Ethanol → ethyl (3RS,4RS)-2-[(1SR,2SR)-2-aminocyclohexyl]-3-(2,4-dichlorophenyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate

HRID 1747047Notes

Reaction equation

HRID 1747047 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[N:8]1[CH:17]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=2[Cl:25])[CH:16]([C:26]([OH:28])=[O:27])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]1=[O:29].[CH2:30](O)[CH3:31].S(=O)(=O)(O)O.C(OCC)(=O)C>O>[NH2:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[N:8]1[CH:17]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=2[Cl:25])[CH:16]([C:26]([O:28][CH2:30][CH3:31])=[O:27])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]1=[O:29]

Participants

6

Reactant 4

HCID 702EthanolHCID 1118Sulfuric AcidHCID 8857Ethyl AcetateHCID 68446722(3RS,4RS)-2-[(1SR,2SR)-2-aminocyclohexyl]-3-(2,4-dichlorophenyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid

Product 1

HCID 72303286ethyl (3RS,4RS)-2-[(1SR,2SR)-2-aminocyclohexyl]-3-(2,4-dichlorophenyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To 4.33 g of (3RS,4RS)-2-[(1SR,2SR)-2-aminocyclohexyl]-3-(2,4-dichlorophenyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid were added 50 ml of ethanol and 2 ml of concentrated sulfuric acid, followed by heating under reflux overnight. Ethyl acetate and water were added thereto to carry out a liquid separation operation, and the organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate and then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate) to obtain 2.3 g of ethyl(3RS,4RS)-2-[(1SR,2SR)-2-aminocyclohexyl]-3-(2,4-dichlorophenyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate as a yellow foam.

Workup

  1. temperatureby heating
  2. temperatureunder reflux overnight
  3. customa liquid separation operation
  4. washthe organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. customevaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate)

Sources & evidence

ORD record
ord-ffc6813961f941c2b2be59026007b4e8
Source dataset
uspto-grants-2015_10
Patent number
US09150541B2

Reaction notes

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