Hydrochloric Acid → Ethyl (3S)-3-hydroxy-3-(6-((methylamino)carbonyl))-2-naphthyl)-3-(1-trityl-1H-imidazil-4-yl) propanoate

HRID 2044779Notes

Reaction equation

HRID 2044779 reaction equation
C(O)C.[OH:4][C@@:5]([C:38]1[CH:47]=[CH:46][C:45]2[C:40](=[CH:41][CH:42]=[C:43]([C:48]([NH:50][CH3:51])=[O:49])[CH:44]=2)[CH:39]=1)([C:14]1[N:15]=[CH:16][N:17]([C:19]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:18]=1)[CH2:6][C:7]([O:9][C:10](C)(C)[CH3:11])=[O:8].Cl.[Cl-].[Na+]>CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4].C(OCC)(=O)C>[OH:4][C@@:5]([C:38]1[CH:47]=[CH:46][C:45]2[C:40](=[CH:41][CH:42]=[C:43]([C:48]([NH:50][CH3:51])=[O:49])[CH:44]=2)[CH:39]=1)([C:14]1[N:15]=[CH:16][N:17]([C:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:18]=1)[CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 5234Sodium ChlorideHCID 57465810tert-butyl(3S)-3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate

Product 1

HCID 57465807Ethyl (3S)-3-hydroxy-3-(6-((methylamino)carbonyl))-2-naphthyl)-3-(1-trityl-1H-imidazil-4-yl) propanoateYield 80%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 8857Ethyl AcetateSolvent

Procedure

150 mL of ethanol and 6.9 mL (23.5 mmol, 3 eq) of titanium tetraisopropoxide were added to 5 g (7.84 mmol) of tert-butyl (3S)-3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate. The mixture was stirred at 60˜65° C. for 28 hours and 40 minutes. 50 mL of 1N hydrochloric acid was added to at 0˜10° C., followed by dilution with 150 mL of ethyl acetate. 50 mL of an aqueous saturated sodium chloride solution was added, and the layers were separated. The organic layer was washed successively with a mixed solution of 25 mL of 1N hydrochloric acid and 65 mL of an aqueous saturated sodium chloride solution two times, 25 mL of an aqueous saturated sodium bicarbonate solution, and 50 mL of an aqueous saturated sodium chloride solution two times. After concentrated under reduced pressure, 50 mL of ethyl acetate, 10 mL of THF and 10 mL of water were added to the concentration residue and the layers were separated. The organic layer was washed with 10 mL of an aqueous saturated sodium chloride solution two times. After concentrated under reduced pressure, 15 mL of IPE was added to the concentrated residue, crystals were loosened, filtered, and washed with 5 mL of IPE two times. Vacuum drying (40° C.) to a constant weight afforded 3.8 g of ethyl (3S)-3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate (yield 80%, enantiomer excess 94.8% ee).

Workup

  1. customthe layers were separated
  2. washThe organic layer was washed successively with a mixed solution of 25 mL of 1N hydrochloric acid and 65 mL of an aqueous saturated sodium chloride solution two times, 25 mL of an aqueous saturated sodium bicarbonate solution, and 50 mL of an aqueous saturated sodium chloride solution two times
  3. concentrationAfter concentrated under reduced pressure, 50 mL of ethyl acetate, 10 mL of THF and 10 mL of water
  4. additionwere added to the concentration residue
  5. customthe layers were separated
  6. washThe organic layer was washed with 10 mL of an aqueous saturated sodium chloride solution two times
  7. concentrationAfter concentrated under reduced pressure, 15 mL of IPE
  8. additionwas added to the concentrated residue, crystals
  9. filtrationfiltered
  10. washwashed with 5 mL of IPE two times
  11. customVacuum drying (40° C.) to a constant weight

Sources & evidence

ORD record
ord-5260c226a46a424b87cbfee58835254b
Source dataset
uspto-grants-2013_11
Patent number
US08586762B2

Reaction notes

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