Trifluoroacetic acid → HCID 66727702, compound

HRID 879972Notes

Reaction equation

HRID 879972 reaction equation
[O:1]([C:8]1[CH:13]=[CH:12][C:11]([S:14]([NH:17][CH2:18][C@H:19]([NH:22]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH2:20][OH:21])(=[O:16])=[O:15])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.C([O-])(O)=O.[Na+].Cl[C:55]([O:57][CH2:58][C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)=[O:56]>C(Cl)(Cl)Cl.CO.CCOC(C)=O>[CH2:58]([O:57][C:55]([NH:22][C@@H:19]([CH2:18][NH:17][S:14]([C:11]1[CH:12]=[CH:13][C:8]([O:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:9][CH:10]=1)(=[O:16])=[O:15])[CH2:20][OH:21])=[O:56])[C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10387Benzyl chloroformateHCID 516892Sodium BicarbonateHCID 66728007HCID 66728007, compound

Product 1

HCID 66727702HCID 66727702, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(S)-3-(4-phenoxybenzenesulfonamido)-2-(tritylamino)propanol (2.26 g, 4.0 mmol) was dissolved in a mixture of chloroform and methanol (1:1, 8 mL) and cooled to 0° C. in an ice bath. The reaction mixture was stirred at 0° C. for 2.5 h, after dropwise addition of trifluoroacetic acid (5.2 mL, 70 mmol). Solvents were removed and the resulting residue was azeotroped 5 times with diethyl ether (5×2 mL) and partitioned between diethyl ether (50 mL) and water (25 mL). The ether layer was washed with water (10 mL) and the combined aqueous fractions are basified with NaHCO3 (1.34 g, 16 mmol). Aqueous fraction was diluted with EtOAc (100 mL) and the mixture was cooled to 0° C. in an ice bath. Then benzyl chloroformate (0.57 mL, 4.0 mmol) was added to the reaction mixture and stirred vigorously at RT for 1.5 h. The layers were separated and the aqueous layer was washed with EtOAc (2×20 mL). The combined organic fractions were washed with brine (20 mL), dried over anhydrous Na2SO4, concentrated and column purified (silica gel, 5% MeOH in EtOAc) to provide (S)-2-(benzyloxycarbonyla-mino)-3-(4-phenoxybenzenesulfonamido) propanol in 76% (1.38 g, 4.0 mmol) yield as colorless solid.

Workup

  1. customSolvents were removed
  2. customthe resulting residue was azeotroped 5 times with diethyl ether (5×2 mL)
  3. custompartitioned between diethyl ether (50 mL) and water (25 mL)
  4. washThe ether layer was washed with water (10 mL)
  5. temperaturethe mixture was cooled to 0° C. in an ice bath
  6. stirringstirred vigorously at RT for 1.5 h
  7. customThe layers were separated
  8. washthe aqueous layer was washed with EtOAc (2×20 mL)
  9. washThe combined organic fractions were washed with brine (20 mL)
  10. dry with materialdried over anhydrous Na2SO4
  11. concentrationconcentrated
  12. customcolumn purified (silica gel, 5% MeOH in EtOAc)

Sources & evidence

ORD record
ord-eaa7ec0fea0a4ac39d054de8fff9cbb7
Source dataset
uspto-grants-2015_03
Patent number
US08993544B2

Reaction notes

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