Hydrogen chloride-ethyl acetate → HCID 178459883, compound

HRID 1953500Notes

Reaction equation

HRID 1953500 reaction equation
Cl.C(OCC)(=O)C.[CH2:8]([O:11][C:12](=[O:47])[NH:13][C@@H:14]([C:22]([N:24]1[CH2:28][CH2:27][CH2:26][C@H:25]1[C:29](=[O:46])[NH:30][CH2:31][C@H:32]1[CH2:37][CH2:36][C@H:35]([NH:38]C(OC(C)(C)C)=O)[CH2:34][CH2:33]1)=[O:23])[C:15]([S:18][CH:19]([CH3:21])[CH3:20])([CH3:17])[CH3:16])[CH2:9][CH3:10]>>[CH2:8]([O:11][C:12](=[O:47])[NH:13][C@@H:14]([C:22]([N:24]1[CH2:28][CH2:27][CH2:26][C@H:25]1[C:29](=[O:46])[NH:30][CH2:31][C@H:32]1[CH2:33][CH2:34][C@H:35]([NH2:38])[CH2:36][CH2:37]1)=[O:23])[C:15]([S:18][CH:19]([CH3:20])[CH3:21])([CH3:16])[CH3:17])[CH2:9][CH3:10]

Participants

3

Reactant 2

HCID 21866389Hydrogen chloride-ethyl acetateHCID 178459886HCID 178459886, compound

Product 1

HCID 178459883HCID 178459883, compoundYield 98.9%

Conditions

Temperature
0 °C

Procedure

1,200 ml of a 4N hydrogenchloride-ethyl acetate solution was added to 200 g of [(S)-1-[(S)-2-[(trans-4-t-butoxycarbonylaminocyclohexylmethyl) carbamoyl]-pyrrolidine-1-carbonyl]-2-isopropylthio-2-methylpropyl]carbamic acid propyl ester prepared by the method as disclosed in Example 1 of WO97/05108, followed by stirring at 0° C. for 1 hour. This solution was concentrated by a rotary evaporator, and to the obtained residue, 1,800 ml of diethyl ether was added, followed by stirring at room temperature. Twenty-four hours later, the solid was collected by filtration and dissolved in 1,000 ml of dichloromethane, and a solution having 25 g of potassium hydroxide dissolved in 400 ml of water, was added thereto. The organic layer was separated, and the aqueous layer was extracted twice with dichloromethane. Then, the organic layer was dried over anhydrous magnesium sulfate. A solution obtained by filtration was concentrated by a rotary evaporator and then dried under reduced pressure of about 5 mmHg at room temperature to obtain 164 g of [(S)-1-[(S)-2-[(trans-4-aminocyclohexylmethyl)carbamoyl]pyrrolidine-1-carbonyl]-2-isopropylthio-2-methylpropyl]carbamic acid propyl ester.

Workup

  1. customprepared by the method
  2. concentrationThis solution was concentrated by a rotary evaporator
  3. additionto the obtained residue, 1,800 ml of diethyl ether was added
  4. stirringby stirring at room temperature
  5. filtrationTwenty-four hours later, the solid was collected by filtration
  6. dissolutiondissolved in 1,000 ml of dichloromethane
  7. dissolutiondissolved in 400 ml of water
  8. additionwas added
  9. customThe organic layer was separated
  10. extractionthe aqueous layer was extracted twice with dichloromethane
  11. dry with materialThen, the organic layer was dried over anhydrous magnesium sulfate
  12. customA solution obtained by filtration
  13. concentrationwas concentrated by a rotary evaporator
  14. customdried under reduced pressure of about 5 mmHg at room temperature

Sources & evidence

ORD record
ord-1e4d18ddc32f4e8aa4602454b4e6a9df
Source dataset
uspto-grants-2000_09
Patent number
US06117897

Reaction notes

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