Hydrochloric Acid → 105637-38-5

HRID 2373068Notes

Reaction equation

HRID 2373068 reaction equation
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

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 6101p-Toluenesulfonic acidHCID 79724-Methylmorpholine2×HCID 8028TetrahydrofuranHCID 62365Isobutyl chloroformateHCID 131717225HCID 131717225, compound

Product 1

HCID 5311161105637-38-5Yield 72%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-15 °C

Procedure

(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).

Workup

  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

Sources & evidence

ORD record
ord-705447845a584b6dbdc5752ec3737b25
Source dataset
uspto-grants-1992_03
Patent number
US05101068

Reaction notes

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