Hydrochloric Acid → (5R)-4-hydroxy-5-(methylamino)-6-phenylhexyl acetate

HRID 849867Notes

Reaction equation

HRID 849867 reaction equation
C(OC(=O)[N:7]([C@H:9]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH:10]([OH:15])[CH2:11][CH2:12][CH2:13][OH:14])[CH3:8])(C)(C)C.Cl.[C:25](OCC)(=[O:27])[CH3:26]>>[C:25]([O:14][CH2:13][CH2:12][CH2:11][CH:10]([OH:15])[C@H:9]([NH:7][CH3:8])[CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)(=[O:27])[CH3:26]

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 8857Ethyl Acetate3×HCID 54277510((1R)-1-benzyl-2,5-dihydroxypentyl)methylcarbamic acid tert-butylester

Product 1

HCID 54296018(5R)-4-hydroxy-5-(methylamino)-6-phenylhexyl acetate

Conditions

Temperature
0 °C

Procedure

((1R)-1-Benzyl-2,5-dihydroxypentyl)methylcarbamic acid tert-butylester (560 mg, 1.52 mmol) was dissolved in ethyl acetate (10 mL). 3M Hydrogen chloride in ethyl acetate (2.0 mL, 6.08 mmol) was added. The solution was stirred at room temp. for 1 h. It was diluted with ethyl acetate (10 mL) and extracted with 1N sodium hydroxide solution (30 mL). The aqueous phase was extracted with ethyl acetate (3×10 mL). The combined organic phases were dried over magnesium sulfate. The solvent was removed in vacuo. The residue was dissolved in dichloromethane (5 mL). The solution was cooled to 0° C. Trifluoroacetic acid (5 mL) was added. The solution was stirred at this temp. for 5 min. The solvents were removed in vacuo. The residue was dissolved in ethyl acetate (10 mL). The solution was extracted with 1N sodium hydroxide solution (10 mL). The aqueous phase was extracted with ethyl acetate (2×5 mL). The combined organic layers were dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (40 g) with dichloromethane/methanol/25% aqueous ammonia 100:10:1 to give 136 mg of (5R)-4-hydroxy-5-(methylamino)-6-phenylhexyl acetate.

Workup

  1. extractionextracted with 1N sodium hydroxide solution (30 mL)
  2. extractionThe aqueous phase was extracted with ethyl acetate (3×10 mL)
  3. dry with materialThe combined organic phases were dried over magnesium sulfate
  4. customThe solvent was removed in vacuo
  5. dissolutionThe residue was dissolved in dichloromethane (5 mL)
  6. additionTrifluoroacetic acid (5 mL) was added
  7. stirringThe solution was stirred at this temp
  8. waitfor 5 min
  9. customThe solvents were removed in vacuo
  10. dissolutionThe residue was dissolved in ethyl acetate (10 mL)
  11. extractionThe solution was extracted with 1N sodium hydroxide solution (10 mL)
  12. extractionThe aqueous phase was extracted with ethyl acetate (2×5 mL)
  13. dry with materialThe combined organic layers were dried over magnesium sulfate
  14. customThe solvent was removed in vacuo
  15. customThe crude product was purified by flash chromatography on silica (40 g) with dichloromethane/methanol/25% aqueous ammonia 100:10:1

Sources & evidence

ORD record
ord-dcb364e0f6a345ffa4ec413ccd19cd02
Source dataset
uspto-grants-2000_01
Patent number
US06013658

Reaction notes

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