Hydrochloric Acid → HCID 131714432, compound

HRID 1583696Notes

Reaction equation

HRID 1583696 reaction equation
C(OC([N:8]1[C@@H:12]([CH2:13][CH:14]([CH3:16])[CH3:15])[CH:11]([CH2:17][N:18](C(OCC2C=CC=CC=2)=O)[C:19](=[O:26])[C@H:20]([CH2:22][CH:23]([CH3:25])[CH3:24])[NH2:21])[O:10]C1(C)C)=O)(C)(C)C.FC(F)(F)C(O)=O.[ClH:46].[H][H]>ClCCl.[Pd].O.C(O)(=O)C>[ClH:46].[ClH:46].[NH2:8][C@@H:12]([CH2:13][CH:14]([CH3:16])[CH3:15])[C@H:11]([OH:10])[CH2:17][NH:18][C:19](=[O:26])[C@H:20]([CH2:22][CH:23]([CH3:24])[CH3:25])[NH2:21]

Participants

9

Reactant 4

HCID 313Hydrochloric Acid2×HCID 6422Trifluoroacetic acidHCID 70443599HCID 70443599, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 131714432HCID 131714432, compoundYield 71.7%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A solution of 250 mg (0.47 mmol) of N-[[(4S)-3-[(t-butyloxy)carbonyl]-2,2-dimethyl-4-(2-methylpropyl)-5-oxazolidinyl]methyl]-N-[(phenylmethoxy)carbonyl]-L-leucinamide in 3 ml of dry dichloromethane was cooled in an ice bath under nitrogen, and treated with 1.5 ml of distilled trifluoroacetic acid. The reaction was stirred at ambient temperature. After 1 hour, the solvent was removed in vacuo, the residue dissolved in 1.7 ml of distilled tetrahydrofuran, treated with 1.0 ml (1 mmol) of 1N hydrochloric acid, and stirred at ambient temperature. After three hours, the reaction was concentrated in vacuo, and the residue was stored in the freezer overnight. The next morning a solution of 259 mg of the free amine hydrochloride from above in 6 ml of a 3:1; acetic acid:water mixture was treated with 1.4 ml (1.4 mmol) of 1N hydrochloric acid, and 150 mg of 10% palladium on charcoal. It was reduced with a steady stream of hydrogen at 1 atmosphere pressure. After 4 hours, filtration of the reaction mixture followed by concentration of the filtrate afforded 242 mg of crude product. The compound was purified by chromatography on a 40 ml column of HP-20 resin, eluted with a gradient from 250 ml of 96:3:1 to 250 ml of 18:2:80, water:1N hydrochloric acid:methanol. The product containing fractions were pooled and concentrated in vacuo then lyophilized from water to obtain 112 mg of the title compound as a 1.3 mole water solvate.

Workup

  1. customthe solvent was removed in vacuo
  2. dissolutionthe residue dissolved in 1.7 ml of distilled tetrahydrofuran
  3. stirringstirred at ambient temperature
  4. waitAfter three hours
  5. concentrationthe reaction was concentrated in vacuo
  6. customwas stored in the freezer overnight
  7. waitAfter 4 hours
  8. filtrationfiltration of the reaction mixture
  9. customafforded 242 mg of crude product
  10. customThe compound was purified by chromatography on a 40 ml column of HP-20 resin
  11. washeluted with a gradient from 250 ml of 96:3
  12. additionThe product containing fractions
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3b6f2222575343d2a71c3aae806f0e4b
Source dataset
uspto-grants-1985_11
Patent number
US04552866

Reaction notes

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