Hydrochloric Acid → Z-FA-FMK

HRID 2373068노트

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HRID 2373068 반응식
C[N:2]1[CH2:7][CH2:6][O:5]CC1.Cl[C:9]([O:11][CH2:12][CH:13]([CH3:15])[CH3:14])=[O:10].[CH3:16][C:17]1[CH:18]=[CH:19][C:20](S(O)(=O)=O)=[CH:21][CH:22]=1.[NH2:27][C@H:28]([C:30]([CH2:32][F:33])=[O:31])[CH3:29].Cl.[CH2:35]1[CH2:39]OC[CH2:36]1>CN(C=O)C>[NH:2]([C:9]([O:11][CH2:12][C:13]1[CH:15]=[CH:39][CH:35]=[CH:36][CH:14]=1)=[O:10])[C@H:7]([C:6]([NH:27][C@H:28]([C:30]([CH2:32][F:33])=[O:31])[CH3:29])=[O:5])[CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

참가 물질

8

반응물 6

HCID 313Hydrochloric AcidHCID 6101p-Toluenesulfonic acidHCID 79724-Methylmorpholine2회HCID 8028TetrahydrofuranHCID 62365Isobutyl chloroformateHCID 131717225HCID 131717225, 화합물

생성물 1

HCID 5311161Z-FA-FMK수율 72%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
-15 °C

실험 절차

(3S)-3-(benzyloxycarbonylphenylalanylamino)-1-fluoro-2-butanone Z-phenylalanine (2.29 g, 7.65 mmol) was dissolved in THF (35 mL). The solution was cooled to -10° C. (methanol/ice bath). N-methylmorpholine (NMM; 0.84 mL, 7.65 mmol) was added, followed by isobutyl chloroformate (IBCF; 0.991 mL, 7.65 mmol), added over 3 minutes. With stirring, in a separate flask cooled to -15° C., p-TsOH.AlaCH2F (2.11 g, 7.65 mmol) was dissolved in DMF (7 mL). This solution was added to the mixed anhydride. NMM (0.84 mL, 7.65 mmol) was added. The reaction mixture was stirred for 45 minutes at between -10° C. and -5° C. 1M HCl (50 mL) was added. The mixture was extracted with ethyl acetate (2×50 mL). The organic phases were combined, washed with saturated aqueous NaHCO3 (2×50 mL), brine (50 mL), dried over MgSO4, filtered, and evaporated to dryness. The crude solid was precipitated from 7:1 hexane/CH2Cl2 (100 mL). After filtration, the solid was recrystallized from isiporpanol, yielding pure Z-Phe-AlaCH2F (2.13 g, 72% from p-TsOH.AlaCH2F).

후처리

  1. additionadded over 3 minutes
  2. stirringThe reaction mixture was stirred for 45 minutes at between -10° C. and -5° C
  3. extractionThe mixture was extracted with ethyl acetate (2×50 mL)
  4. washwashed with saturated aqueous NaHCO3 (2×50 mL), brine (50 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe crude solid was precipitated from 7:1 hexane/CH2Cl2 (100 mL)
  9. filtrationAfter filtration
  10. customthe solid was recrystallized from isiporpanol

출처 및 근거

ORD 기록
ord-705447845a584b6dbdc5752ec3737b25
출처 데이터셋
uspto-grants-1992_03
특허 번호
US05101068

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