Trifluoroacetic acid → HCID 117738858, compound

HRID 1754856Notes

Reaction equation

HRID 1754856 reaction equation
NC(N)=S.[C:5]([NH:8][C:9]1[CH:10]=[CH:11][C:12]([F:31])=[C:13]([C@@:15]2([NH:23]C(=O)OC(C)(C)C)[C@:19]([F:22])([CH2:20][OH:21])[CH2:18][O:17][CH2:16]2)[CH:14]=1)(=[O:7])[CH3:6].FC(F)(F)C(O)=O.C(N(CC)CC)C.[C:46]([N:54]=[C:55]=[S:56])(=[O:53])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1>ClCCl>[C:5]([NH:8][C:9]1[CH:10]=[CH:11][C:12]([F:31])=[C:13]([C@@:15]2([NH:23][C:55]([NH:54][C:46](=[O:53])[C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)=[S:56])[C@:19]([F:22])([CH2:20][OH:21])[CH2:18][O:17][CH2:16]2)[CH:14]=1)(=[O:7])[CH3:6]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 68284Benzoyl isothiocyanateHCID 2723790ThioureaHCID 117738639HCID 117738639, compound

Product 1

HCID 117738858HCID 117738858, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Scheme 2, step I, (deprotection and thiourea formation): A solution of tert-butyl N-[(3S,4S)-3-(5-acetamido-2-fluoro-phenyl)-4-fluoro-4-(hydroxymethyl)tetrahydrofuran-3-yl]carbamate (2.70 g, 6.99 mmol) in dichloromethane (40 mL) and trifluoroacetic acid (8.00 mL, 106 mmol) is stirred at ambient temperature for 150 minutes. The reaction is concentrated under reduced pressure and azeotroped with toluene. The residue is dissolved in tetrahydrofuran and treated with triethylamine (1.10 mL, 7.89 mmol) and benzoyl isothiocyanate (1.00 mL, 7.41 mmol). The reaction is stirred at ambient temperature for 16.5 hours and is then quenched with a solution of saturated sodium bicarbonate in water, extracted with ethyl acetate and dichloromethane consecutively. The organic layers are combined, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to give a residue. The residue is purified by silica gel flash chromatography, eluting with methanol/dichloromethane (0:10) to methanol/dichloromethane (1:10) to give the title compound (2.60 g, 83%). ES/MS (m/e): 450 (M+1).

Workup

  1. concentrationThe reaction is concentrated under reduced pressure
  2. customazeotroped with toluene
  3. dissolutionThe residue is dissolved in tetrahydrofuran
  4. customis then quenched with a solution of saturated sodium bicarbonate in water
  5. extractionextracted with ethyl acetate and dichloromethane consecutively
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give a residue
  10. customThe residue is purified by silica gel flash chromatography
  11. washeluting with methanol/dichloromethane (0:10) to methanol/dichloromethane (1:10)

Sources & evidence

ORD record
ord-81fe2e36dc5542419e1246141d603468
Source dataset
uspto-grants-2015_10
Patent number
US09169271B2

Reaction notes

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