Hydrochloric Acid → 6-[(1S)-1,3-Dihydroxy-1-[1-(triphenylmethyl)-1H-imidazol-4-yl]propyl]-N-methyl-2-naphthalenecarboxamide

HRID 2044772Notes

Reaction equation

HRID 2044772 reaction equation
[BH4-].[Na+].[Cl-].[Ca+2].[Cl-].[OH:6][C@@:7]([C:37]1[CH:46]=[CH:45][C:44]2[C:39](=[CH:40][CH:41]=[C:42]([C:47]([NH:49][CH3:50])=[O:48])[CH:43]=2)[CH:38]=1)([C:13]1[N:14]=[CH:15][N:16]([C:18]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:17]=1)[CH2:8][C:9](OC)=[O:10].Cl>C(OCC)(=O)C.O.C1COCC1.C(O)C>[OH:6][C@@:7]([C:37]1[CH:38]=[C:39]2[C:44](=[CH:45][CH:46]=1)[CH:43]=[C:42]([C:47]([NH:49][CH3:50])=[O:48])[CH:41]=[CH:40]2)([C:13]1[N:14]=[CH:15][N:16]([C:18]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:17]=1)[CH2:8][CH2:9][OH:10]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 5284359Calcium ChlorideHCID 57465809methyl (3S)-3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate

Product 1

HCID 574658086-[(1S)-1,3-Dihydroxy-1-[1-(triphenylmethyl)-1H-imidazol-4-yl]propyl]-N-methyl-2-naphthalenecarboxamideYield 90%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

0.095 g (2.51 mmol, 8 eq) of sodium borohydride was added to 1.3 mL of ethanol and 1.3 mL of THF. 0.14 g (1.26 mmol, 4 eq) of calcium chloride was added at 0˜5° C., and the mixture was stirred at the same temperature for 30 minutes. 0.188 g (0.314 mmol) of methyl (3S)-3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate was added at 0˜5° C., and the mixture was stirred for 30 minutes. The mixture was stirred at room temperature for 4.5 hours. 7 mL of water was added dropwise at 35° C. or lower. 2.5 mL of 1N hydrochloric acid was added dropwise, followed by dilution with 10 mL of ethyl acetate. Then, the layers were separated. The organic layer was washed successively with 2 mL of an aqueous saturated sodium bicarbonate solution and 2 mL of an aqueous saturated sodium chloride solution. After concentrated under reduced pressure, the concentration residue was loosened with 2 mL of IPE, crystals were filtered, and washed with 1 mL of IPE. Vacuum drying (40° C.) to a constant weight afforded 0.16 g of 6-[(1S)-1,3-dihydroxy-1-(1-trityl-1H-imidazol-4-yl)propyl]-N-methyl-2-naphthamide (yield 90%).

Workup

  1. stirringthe mixture was stirred for 30 minutes
  2. stirringThe mixture was stirred at room temperature for 4.5 hours
  3. customThen, the layers were separated
  4. washThe organic layer was washed successively with 2 mL of an aqueous saturated sodium bicarbonate solution and 2 mL of an aqueous saturated sodium chloride solution
  5. concentrationAfter concentrated under reduced pressure
  6. filtrationwere filtered
  7. washwashed with 1 mL of IPE
  8. customVacuum drying (40° C.) to a constant weight

Sources & evidence

ORD record
ord-a640acaacae54bd08288bfd17f21019e
Source dataset
uspto-grants-2013_11
Patent number
US08586762B2

Reaction notes

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