Hydrochloric Acid → HCID 67004551, compound

HRID 1678096Notes

Reaction equation

HRID 1678096 reaction equation
O.C[O:3][C:4](=[O:27])[CH2:5][C@@H:6]([OH:26])[C@H:7]([N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH3:18])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]([Cl:16])[CH:10]=1.O.[OH-].[Li+].Cl>C1(C)C=CC=CC=1>[C:22]([O:21][C:19]([N:17]([CH3:18])[C@H:7]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]([Cl:16])[CH:10]=1)[C@H:6]([OH:26])[CH2:5][C:4]([OH:27])=[O:3])=[O:20])([CH3:25])([CH3:24])[CH3:23]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 67005161HCID 67005161, compound

Product 1

HCID 67004551HCID 67004551, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
20 °C

Procedure

Water (3 ml) is added to the stirred reaction mixture containing (3R,4R)-4-(tert-butoxy-carbonyl-methyl-amino)-5-(3,4-dichloro-phenyl)-3-hydroxy-pentanoic acid methyl ester (5) at 18-22° C., then lithium hydroxide monohydrate (0.755 g, 18 mmol) is added. Stirring at 18-22° C. is continued for approx. 2 hours. Hydrochloric acid (approx. 12.6 ml of 2N, 25.2 mmol)) is added over a period of approx. 30 minutes, until pH 1.7-2.2 is obtained. Toluene (12 ml) is added to the stirred mixture and stirring at 18-22° C. is continued for approx. 10 minutes. Stirring is stopped and the layers are allowed to separate. The lower, aqueous layer is separated and the upper, organic layer is extracted with water (12 ml). Stirring is stopped and the lower, aqueous layer is separated. The organic layer is filtrated over a filter charged with anhydrous sodium sulfate (3 g) in order to remove remains of water and 1,3-dicyclohexyl urea, the latter originating from step 1. The filter cake is rinsed with toluene (2 ml), then N,N-dimethylformamide (12 ml) is added to the filtrate. The resulting solution is concentrated by distilling toluene at a mantle temperature of approx. 50° C. under reduced pressure, until the volume of the residue is approx. 14 ml. This resulting solution, containing (3R,4R)-4-(tert-butoxycarbonyl-methyl-amino)-5-(3,4-dichloro-phenyl)-3-hydroxy-pentanoic acid (6) is used as such in the following step.

Workup

  1. customis obtained
  2. stirringstirring at 18-22° C.
  3. waitis continued for approx. 10 minutes
  4. stirringStirring
  5. customto separate
  6. customThe lower, aqueous layer is separated
  7. extractionthe upper, organic layer is extracted with water (12 ml)
  8. stirringStirring
  9. customthe lower, aqueous layer is separated
  10. filtrationThe organic layer is filtrated over a filter
  11. additioncharged with anhydrous sodium sulfate (3 g) in order
  12. customto remove remains of water and 1,3-dicyclohexyl urea
  13. washThe filter cake is rinsed with toluene (2 ml)
  14. additionN,N-dimethylformamide (12 ml) is added to the filtrate
  15. concentrationThe resulting solution is concentrated
  16. distillationby distilling toluene at a mantle temperature of approx. 50° C. under reduced pressure
  17. additionThis resulting solution, containing (3R,4R)-4-(tert-butoxycarbonyl-methyl-amino)-5-(3,4-dichloro-phenyl)-3-hydroxy-pentanoic acid (6)

Sources & evidence

ORD record
ord-e9b78d7feeb741e4938360c3cb4d5456
Source dataset
uspto-grants-2011_08
Patent number
US08008479B2

Reaction notes

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