Trifluoroacetic acid → HCID 86661747, compound

HRID 879970Notes

Reaction equation

HRID 879970 reaction equation
[CH:1]([O:4][P:5]([C:11]([NH:13][CH2:14][C@H:15]([NH:18]C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[CH2:16][OH:17])=[O:12])([O:7][CH:8]([CH3:10])[CH3:9])=[O:6])([CH3:3])[CH3:2].FC(F)(F)C(O)=O.C([O-])(O)=O.[Na+].Cl[C:51]([O:53][CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)=[O:52]>C(Cl)(Cl)Cl.CO.CCOC(C)=O>[CH2:54]([O:53][C:51]([NH:18][C@@H:15]([CH2:14][NH:13][C:11]([P:5]([O:7][CH:8]([CH3:10])[CH3:9])([O:4][CH:1]([CH3:3])[CH3:2])=[O:6])=[O:12])[CH2:16][OH:17])=[O:52])[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10387Benzyl chloroformateHCID 516892Sodium BicarbonateHCID 86661746HCID 86661746, compound

Product 1

HCID 86661747HCID 86661747, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21584188Chloroform methanolSolvent

Conditions

Temperature
0 °C

Procedure

(S)-3-diisopropylphosphonoformamido-2-(tritylamino)propanol (10.49 g, 20 mmol) was dissolved in a mixture of chloroform-methanol (1:1, 40 mL) and cooled to 0° C. in an ice bath. The reaction mixture was stirred at RT for 7 h, after dropwise addition of trifluoroacetic acid (20.0 mmol, 1.5 mL) at 0° C. The solvents were removed and the resulting residue was azeotroped 5 times with diethyl ether (5×40 mL) and partitioned between diethyl ether (150 mL) and water (50 mL). The ether layer was washed with water (20 mL) and the combined aqueous fractions were basified with NaHCO3 (80 mmol, 6.72 g). Aqueous fraction was diluted with EtOAc (150 mL) and the mixture was cooled to 0° C. in an ice bath. Benzyl chloroformate (2.9 mL, 20 mmol) was then added to the reaction mixture at 0° C. and stirred vigorously at RT for 1.5 h. The layers were separated and the aqueous layer was washed with EtOAc (2×30 mL). The combined organic fractions were washed with brine (40 mL), dried over anhydrous Na2SO4 and concentrated. The residue was purified by column chromatography (silica gel, 5% MeOH in EtOAc) to afford (S)-2-benzyloxycarbonylamino 3-(diisopropy-lphosphonoformamido)propanol as gummy solid in 50% (4.16 g) yield.

Workup

  1. customThe solvents were removed
  2. customthe resulting residue was azeotroped 5 times with diethyl ether (5×40 mL)
  3. custompartitioned between diethyl ether (150 mL) and water (50 mL)
  4. washThe ether layer was washed with water (20 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 (2×30 mL)
  9. washThe combined organic fractions were washed with brine (40 mL)
  10. dry with materialdried over anhydrous Na2SO4
  11. concentrationconcentrated
  12. customThe residue was purified by column chromatography (silica gel, 5% MeOH in EtOAc)

Sources & evidence

ORD record
ord-c8374a37b7264ccc9fe0b1337b2a918b
Source dataset
uspto-grants-2015_03
Patent number
US08993544B2

Reaction notes

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