Trifluoroacetic acid → HCID 86673301, compound

HRID 1192736Notes

Reaction equation

HRID 1192736 reaction equation
[F:1][C:2]([F:39])([F:38])[CH:3]([NH:11][C@@H:12]([CH2:17][S:18]C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[C:13]([O:15][CH3:16])=[O:14])[C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][CH:5]=1.FC(F)(F)C(O)=O.C([SiH](CC)CC)C>ClCCl>[SH:18][CH2:17][C@H:12]([NH:11][CH:3]([C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][CH:5]=1)[C:2]([F:1])([F:38])[F:39])[C:13]([O:15][CH3:16])=[O:14]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 70945785HCID 70945785, compound

Product 1

HCID 86673301HCID 86673301, compoundYield 84.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (2R)-methyl 2-((2,2,2-trifluoro-1-(4-fluorophenyl)ethyl)amino)-3-(tritylthio)propanoate (24.8 g; 44.8 mmol) in anhydrous dichloromethane (200 mL), previously cooled to in an ice-water bath under nitrogen, was added trifluoroacetic acid (14 mL; 20.7 g; 182 mmol; 405 mole %), followed by triethylsilane (14.4 mL; 10.5 g; 90.1 mmol; 200 mole %). The reaction mixture was stirred at ambient temperature for 2 h then concentrated in vacuo. The residue was redistilled from dichloromethane and the residue absorbed onto silica gel (30 g). The absorbed sample was applied to a column of SiO2 (660 g) and eluted with 2% ethyl acetate in hexane, gradually increased to 10% EtOAc in hexane to give 11.74 g (84.5%) of (2R)-methyl 3-mercapto-2-((2,2,2-trifluoro-1-(4-fluorophenyl)ethyl)amino)propanoate which was used directly in the next step. LC-MS, negative ion mode: m/z=310 [M−H]− (100%).

Workup

  1. concentrationthen concentrated in vacuo
  2. distillationThe residue was redistilled from dichloromethane
  3. customthe residue absorbed onto silica gel (30 g)
  4. washeluted with 2% ethyl acetate in hexane
  5. temperaturegradually increased to 10% EtOAc in hexane

Sources & evidence

ORD record
ord-12e47c58c1c24e89900481fb794a93f3
Source dataset
uspto-grants-2014_03
Patent number
US08680152B2

Reaction notes

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