Trifluoroacetic acid → HCID 72533146, compound

HRID 2245406Notes

Reaction equation

HRID 2245406 reaction equation
[OH:1][CH2:2][C@@H:3]([NH:8][C:9]([CH:11]1[CH2:16][S:15][CH2:14][CH2:13][N:12]1[C:17]([O-:19])=O)=[O:10])C(OC)=O.C(O)(C(F)(F)F)=O>ClCCl>[OH:1][CH2:2][CH:3]1[C:17](=[O:19])[N:12]2[CH:11]([CH2:16][S:15][CH2:14][CH2:13]2)[C:9](=[O:10])[NH:8]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 131727994HCID 131727994, compound

Product 1

HCID 72533146HCID 72533146, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the crude 1,1-dimethylethyl (3R or S)-({[(1R)-1-(hydroxymethyl)-2-(methyloxy)-2-oxoethyl]amino}carbonyl)-4-thiomorpholinecarboxylate (D26) in 20 mL of dichloromethane were added 10 mL of TFA. The reaction mixture was stirred at room temperature for 4 hrs. The solvent was removed under reduced pressure and the residue was taken up in MeOH and loaded on a SCX cartridge. The fractions eluted with methanolic ammonia were collected, the volume was reduced and the solution was stirred at 50° C. for 45 min. Then it was irradiated three times by microwave [set parameters: T=80° C., t=10 min (1×); T=120° C., t=5 min (2×)]. The solvent was removed and after 2 days the crude revealed the formation of a white solid. So it was precipitated with DME and it was collected by filtration, washing with Et2O, to give the 1st batch of the title compound (120 mg, y=28% over 2 steps). The filtered solution was evaporated to dryness and the resulting crude, dissolved in DME, was irradiated two times by microwave (set parameters: T=130° C., t=30 min). After filtration, the 2nd batch of the title compound was isolated as a brownish solid (94 mg, y=22% over 2 steps). The filtered solution was treated in the same way as before and after four microwave irradiation [set parameters: T=130° C., t=30 min (3×) and t=90 min (1×)] the 3rd batch of the title compound was isolated as a brownish solid (50 mg, y=12% over 2 steps).

Workup

  1. customThe solvent was removed under reduced pressure
  2. washThe fractions eluted with methanolic ammonia
  3. customwere collected
  4. stirringthe solution was stirred at 50° C. for 45 min
  5. customThen it was irradiated three times by microwave [set parameters: T=80° C., t=10 min (1×); T=120° C., t=5 min (2×)]
  6. customThe solvent was removed and after 2 days the crude
  7. customSo it was precipitated with DME and it
  8. filtrationwas collected by filtration
  9. washwashing with Et2O

Sources & evidence

ORD record
ord-98b5784fade64ba6a8911febcc85c66d
Source dataset
uspto-grants-2010_03
Patent number
US07683056B2

Reaction notes

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