Trifluoroacetic acid → HCID 58169849, compound

HRID 384018Notes

Reaction equation

HRID 384018 reaction equation
[F:1][C:2]([F:49])([F:48])[C:3]1[CH:4]=[C:5]([C@H:13]([N:15]([CH3:47])[C:16]([N:18]2[CH2:23][CH2:22][C@@:21]([CH2:31][CH2:32][C:33](=O)[C:34]([O:36][CH3:37])=[O:35])([NH:24]S(C(C)(C)C)=O)[CH2:20][C@@H:19]2[C:39]2[CH:44]=[CH:43][C:42]([F:45])=[CH:41][C:40]=2[CH3:46])=[O:17])[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C(O)(C(F)(F)F)=O.C([SiH](CC)CC)C.C([O-])(O)=O.[Na+]>C(Cl)Cl>[F:48][C:2]([F:1])([F:49])[C:3]1[CH:4]=[C:5]([C@H:13]([N:15]([CH3:47])[C:16]([N:18]2[CH2:23][CH2:22][C@@:21]3([NH:24][CH:33]([C:34]([O:36][CH3:37])=[O:35])[CH2:32][CH2:31]3)[CH2:20][C@@H:19]2[C:39]2[CH:44]=[CH:43][C:42]([F:45])=[CH:41][C:40]=2[CH3:46])=[O:17])[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 516892Sodium BicarbonateHCID 86651616HCID 86651616, compound2×

Product 1

HCID 58169849HCID 58169849, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

To a solution of Methyl 4-[(2R,4R)-1-{[{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}(methyl)amino]carbonyl}-4-{[(1,1-dimethylethyl)sulfinyl]amino}-2-(4-fluoro-2-methylphenyl)-4-piperidinyl]-2-oxobutanoate (Intermediate 6, 62 mg, 0.086 mmol) in DCM (1 mL) was added TFA (4 mL, 51.9 mmol) and the reaction mixture was stirred at 25° C. for 6 hrs. Triethylsilane (1 mL, 6.26 mmol, Aldrich) was added to the reaction mixture and it was stirred for 1 hr. The reaction mixture was left still overnight and the day after it was poured very carefully in a NaHCO3 saturated solution to be neutralised and DCM was added. The two phases were separated, the aqueous layer was extracted with DCM (3×) and the combined organic phases were dried and evaporated to dryness. The crude was purified by flash chromatography on silica with SP1 (Biotage) system (from 1:0 to 0:1 Cyclohexane/EtOAc) to give the two diastereoisomers:

Workup

  1. stirringwas stirred for 1 hr
  2. waitThe reaction mixture was left still overnight
  3. customThe two phases were separated
  4. extractionthe aqueous layer was extracted with DCM (3×)
  5. customthe combined organic phases were dried
  6. customevaporated to dryness
  7. customThe crude was purified by flash chromatography on silica with SP1 (Biotage) system (from 1:0 to 0:1 Cyclohexane/EtOAc)
  8. customto give the two diastereoisomers

Sources & evidence

ORD record
ord-079ca5df81954985bfe9d2d46b7fa200
Source dataset
uspto-grants-2013_02
Patent number
US08367692B2

Reaction notes

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