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

HRID 420224노트

반응식

HRID 420224 반응식
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]

참가 물질

9

반응물 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

생성물 1

HCID 574658086-[(1S)-1,3-Dihydroxy-1-[1-(triphenylmethyl)-1H-imidazol-4-yl]propyl]-N-methyl-2-naphthalenecarboxamide수율 58%

시약·촉매·용매 4

HCID 3007855Zincchloride촉매HCID 702Ethanol용매HCID 962Water용매3회HCID 8857Ethyl Acetate용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-814799891a6544ec88288b93d2c31a53
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08093403B2

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