Acetic Acid → N-[3,3,3-trifluoro-2-(mercaptomethyl)-1-oxopropyl]-L-tryptophan

HRID 36501

Reaction equation

HRID 36501 reaction equation
C([S:4][CH2:5][CH:6]([C:24]([F:27])([F:26])[F:25])[C:7]([NH:9][C@H:10]([C:21]([OH:23])=[O:22])[CH2:11][C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[NH:14][CH:13]=1)=[O:8])(=O)C.S([O-])(O)(=O)=O.[K+].C(OCC)(=O)C.C(O)(=O)C>[OH-].[NH4+].O.CO>[F:27][C:24]([F:25])([F:26])[CH:6]([CH2:5][SH:4])[C:7]([NH:9][C@H:10]([C:21]([OH:23])=[O:22])[CH2:11][C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[NH:14][CH:13]=1)=[O:8]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 8857Ethyl AcetateHCID 516920Potassium bisulfateHCID 54017298N-[2-[(Acetylthio)methyl]-3,3,3-trifluoro-1-oxopropyl]-L-tryptophan

Product 1

HCID 9928817N-[3,3,3-trifluoro-2-(mercaptomethyl)-1-oxopropyl]-L-tryptophan

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 14923Ammonium HydroxideSolvent

Procedure

A suspension of the product of Example 7 (2.6 g., 6.5 mmol.) in 4.25 mL of concentrated ammonium hydroxide and 9.3 mL of water was stirred at room temperature under argon for 12-15 minutes. The resulting solution was acidified with 200 mL of 5% potassium hydrogen sulfate and extracted with ethyl acetate (5×50 mL). The combined ethyl acetate extract was washed with brine, dried (MgSO4) and evaporated to give 2.4 g. of a light yellow solid. This material was combined with an additional 80 mg. of compound and flash chromatographed on 300 g. of silica gel eluting with methylene chloride:methanol:acetic acid, 40:1:1 to give 2.3 g. of white solid. This solid was triturated with toluene containing approximately 5% ethyl acetate, and 1.25 g. of white crystalline solid was collected by filtration. The filtrate was evaporated to dryness and the residue was triturated in a similar fashion to produce an additional 560 mg. of material which was combined with the initial 1.25 g. crop to yield 1.81 g. of title isomer A compound as a white crystalline solid; m.p. 148.5°-150.5° C., TLC Rf =0.48 (300:100:1 ethyl acetate:hexanes:acetic acid), [α]D =-10.3° (c=1.00, methanol).

Workup

  1. extractionextracted with ethyl acetate (5×50 mL)
  2. extractionThe combined ethyl acetate extract
  3. washwas washed with brine
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customto give 2.4 g
  7. customof compound and flash chromatographed on 300 g
  8. customof silica gel eluting with methylene chloride:methanol:acetic acid, 40:1:1 to give 2.3 g
  9. customThis solid was triturated with toluene containing approximately 5% ethyl acetate, and 1.25 g
  10. filtrationof white crystalline solid was collected by filtration
  11. customThe filtrate was evaporated to dryness
  12. customthe residue was triturated in a similar fashion
  13. customto produce an additional 560 mg
  14. customcrop to yield 1.81 g

Sources & evidence

ORD record
ord-823edff766d44fab89ef4616b49a594b
Source dataset
uspto-grants-1995_05
Patent number
US05414013

Linked notes

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