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

HRID 420224Notes

Reaction equation

HRID 420224 reaction equation
C1COCC1.[BH4-].[Na+].[OH:8][C@@:9]([C:42]1[CH:51]=[CH:50][C:49]2[C:44](=[CH:45][CH:46]=[C:47]([C:52]([NH:54][CH3:55])=[O:53])[CH:48]=2)[CH:43]=1)([C:18]1[N:19]=[CH:20][N:21]([C:23]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:22]=1)[CH2:10][C:11](OC(C)(C)C)=[O:12].[Cl-].[NH4+]>C(OCC)(=O)C.C(O)C.O.[Cl-].[Zn+2].[Cl-]>[OH:8][C@@:9]([C:42]1[CH:43]=[C:44]2[C:49](=[CH:50][CH:51]=1)[CH:48]=[C:47]([C:52]([NH:54][CH3:55])=[O:53])[CH:46]=[CH:45]2)([C:18]1[N:19]=[CH:20][N:21]([C:23]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:22]=1)[CH2:10][CH2:11][OH:12]

Participants

9

Reactant 4

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 4311764Sodium borohydrideHCID 57465810tert-butyl(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 58%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 702EthanolSolventHCID 962WaterSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

15 mL of THF was added to 0.47 g (12.5 mmol, 8 eq) of sodium borohydride. 0.85 g (6.27 mmol, 4 eq) of zinc chloride was added at 30° C., and the mixture was stirred at 35˜37° C. for 15 minutes. 1 g (1.57 mmol) of tert-butyl (3S)-3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate was added at 35° C. The mixture was stirred at 45˜49° C. for 24 hours and 30 minutes. 5 mL of water was added dropwise at 35° C. or lower. 15 mL of water and 5 mL of an aqueous saturated ammonium chloride solution were added, and the mixture was stirred at 20˜25° C. for 6 hours. After diluted with 50 mL of ethyl acetate, 10 mL of ethanol and 10 mL of water, insoluble materials were filtered. The filtrate was separated, and the organic layer was washed successively with 20 mL of water and 20 mL of an aqueous saturated sodium chloride solution. After concentrated under reduced pressure, 1 mL of ethyl acetate and 2 mL of IPE were added to the concentration residue, crystals were loosened, filtered, and washed with 1.25 mL of ethyl acetate/IPE=1/1 two times. Vacuum drying (40° C.) to a constant weight afforded 0.48 g of 6-[(1S)-1,3-dihydroxy-1-(1-trityl-1H-imidazol-4-yl)propyl]-N-methyl-2-naphthamide (yield 58%).

Workup

  1. stirringThe mixture was stirred at 45˜49° C. for 24 hours and 30 minutes
  2. stirringthe mixture was stirred at 20˜25° C. for 6 hours
  3. filtrationwere filtered
  4. customThe filtrate was separated
  5. washthe organic layer was washed successively with 20 mL of water and 20 mL of an aqueous saturated sodium chloride solution
  6. concentrationAfter concentrated under reduced pressure, 1 mL of ethyl acetate and 2 mL of IPE
  7. additionwere added to the concentration residue, crystals
  8. filtrationfiltered
  9. washwashed with 1.25 mL of ethyl acetate/IPE=1/1 two times
  10. customVacuum drying (40° C.) to a constant weight

Sources & evidence

ORD record
ord-814799891a6544ec88288b93d2c31a53
Source dataset
uspto-grants-2012_01
Patent number
US08093403B2

Reaction notes

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