Ethyl Acetate → N-[3,3,3-Trifluoro-2-(mercaptomethyl)-1-oxopropyl]-L-leucine

HRID 1589060

Reaction equation

HRID 1589060 reaction equation
C([S:4][CH2:5][CH:6]([C:18]([F:21])([F:20])[F:19])[C:7]([NH:9][C@H:10]([C:15]([OH:17])=[O:16])[CH2:11][CH:12]([CH3:14])[CH3:13])=[O:8])(=O)C.S([O-])(O)(=O)=O.[K+].C(OCC)(=O)C>[OH-].[NH4+].O.CO.C(O)(=O)C.CCCCCC>[F:19][C:18]([F:20])([F:21])[CH:6]([CH2:5][SH:4])[C:7]([NH:9][C@H:10]([C:15]([OH:17])=[O:16])[CH2:11][CH:12]([CH3:14])[CH3:13])=[O:8]

Participants

9

Reactant 3

HCID 8857Ethyl Acetate2×HCID 516920Potassium bisulfateHCID 54059189N-[2-[(Acetylthio)methyl]-3,3,3-trifluoro-1-oxopropyl]-L-leucine

Product 1

HCID 53740741N-[3,3,3-Trifluoro-2-(mercaptomethyl)-1-oxopropyl]-L-leucine

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolvent2×HCID 887MethanolSolventHCID 962WaterSolventHCID 8058HexaneSolventHCID 14923Ammonium HydroxideSolvent

Procedure

A suspension of the product of Example 18 (2.3 g., 6.98 mmol.) in 4.45 mL of concentrated ammonium hydroxide and 10 mL of water was stirred at room temperature under argon for 8 minutes. The resulting clear solution was acidified with 5% potassium hydrogen sulfate solution to pH 2 and extracted with 100 mL of ethyl acetate followed by 3×75 mL of additional extractions. The combined ethyl acetate extract was washed with 100 mL of brine, dried (MgSO4) and evaporated to give 1.94 g. of an off-white solid. Flash chromatography on 200 g. of silica gel eluting with ethyl acetate:hexanes:acetic acid, 100:100:1 afforded 1.72 g. of the title isomer A product as a white crystalline solid, m.p. 143°-145° C., TLC Rf =0.38 (100:50:1 ethyl acetate:hexane:acetic acid), [α]D =-62.2° (c=1.00, methanol).

Workup

  1. extractionextracted with 100 mL of ethyl acetate
  2. extractionfollowed by 3×75 mL of additional extractions
  3. extractionThe combined ethyl acetate extract
  4. washwas washed with 100 mL of brine
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customto give 1.94 g

Sources & evidence

ORD record
ord-95ad3ec5cfeb498ab23de63c89c2a185
Source dataset
uspto-grants-1993_06
Patent number
US05223516

Linked notes

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