Hydrochloric Acid → Z-FA-FMK

HRID 248587ノート

反応式

HRID 248587 の反応式
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

参加物

8

反応物 6

HCID 313Hydrochloric AcidHCID 6101p-Toluenesulfonic acidHCID 79724-Methylmorpholine2 回HCID 8028TetrahydrofuranHCID 62365Isobutyl chloroformateHCID 131717225HCID 131717225、化合物

生成物 1

HCID 5311161Z-FA-FMK収率 72%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
-15 °C

実験手順

(3S)-3-(benzyloxycarbonylphenylalanylamino)-1-fluoro-2-butanone Z-phenylalanine (2.29 g, 7.65 mmol) was 5 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).

後処理

  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

出典と根拠

ORDレコード
ord-fe01cd3d480046bbac0eea4c5b4f1224
出典データセット
uspto-grants-1993_05
特許番号
US05210272

反応ノート

読み込み中…