Trifluoroacetic acid → HCID 178523578, compound

HRID 1263527Notes

Reaction equation

HRID 1263527 reaction equation
[C:1]1([O:7][C:8](Cl)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[Si]([O:25][C:26]1[CH:31]=[C:30]([O:32][Si](C(C)(C)C)(C)C)[CH:29]=[CH:28][C:27]=1[C@H:40]1[CH2:45][CH2:44][C@H:43]([NH2:46])[CH2:42][CH2:41]1)(C(C)(C)C)(C)C.FC(F)(F)C(O)=O>CN(C)C1C=CN=CC=1.ClC(Cl)C.ClCCl.C1(C)C=CC=CC=1.O>[C:1]1([O:7][C:8](=[O:9])[NH:46][C@H:43]2[CH2:42][CH2:41][C@H:40]([C:27]3[CH:28]=[CH:29][C:30]([OH:32])=[CH:31][C:26]=3[OH:25])[CH2:45][CH2:44]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

10

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 178455052HCID 178455052, compound

Product 1

HCID 178523578HCID 178523578, compoundYield 40.2%

Reagents, catalysts & solvents 5

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Procedure

A solution of phenylchloroformate (0.045 ml, 0.36 mmol), triethylamine (0.085 ml), 4-dimethylaminopyridine (catalytic) and trans-4-(2,4-bis{[tert-butyl(dimethyl)silyl]oxy}phenyl) cyclohexylamine (0.043 g) in dichloroethane (11 ml) was stirred at room temperature for 60 hr. The mixture was partitioned between saturated aqueous sodium carbonate (15 ml) and dichloromethane (15 ml). The aqueous phase was extracted with dichloromethane (2×15 ml) and the combined organic extracts washed with brine (20 ml), dried over magnesium sulfate, filtered and concentrated in vacuo. Purification via flash chromatography (SiO2, ethyl acetate/petroleum ether) afforded a colourless gum. This was dissolved in dichloromethane (15 ml) and warmed with a mixture of water (7.5 ml) and trifluoroacetic acid (7.5 ml) at 80° C. for 17 hr. On cooling, toluene (25 ml) was added and the solution concentrated in vacuo. Methanol (25 ml) was added and the solution again concentrated in vacuo. Purification via flash chromatography (SiO2, ethyl acetate/petroleum ether) afforded the title compound (0.013 g, 13%) as a colourless solid. δH (CD3OD) 1.44-1.63 (4H, m), 1.96 (2H, m), 2.13 (2H, m), 2.86 (1H, m), 3.55 (1H, m), 6.30 (2H, m), 6.92 (1H, d), 7.12 (2H, m), 7.22 (1H, m) and 7.40 (2H, m); m/s(ES+) 328.26 (M+H)+.

Workup

  1. customThe mixture was partitioned between saturated aqueous sodium carbonate (15 ml) and dichloromethane (15 ml)
  2. extractionThe aqueous phase was extracted with dichloromethane (2×15 ml)
  3. washthe combined organic extracts washed with brine (20 ml)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification via flash chromatography (SiO2, ethyl acetate/petroleum ether)
  8. customafforded a colourless gum
  9. temperatureOn cooling
  10. concentrationthe solution concentrated in vacuo
  11. additionMethanol (25 ml) was added
  12. concentrationthe solution again concentrated in vacuo
  13. customPurification via flash chromatography (SiO2, ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-918ba18fa27a4f76bb6bcd718fc4399e
Source dataset
uspto-grants-2003_04
Patent number
US06541473B2

Reaction notes

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