2-Fluoroethylamine → (2S,3R,4R,5S,6R)-6-(acetoxymethyl)-3-(3-(2-fluoroethyl)thioureido)-tetrahydro-2H-pyran-2,4,5-triyl triacetate

HRID 1854246Notes

Reaction equation

HRID 1854246 reaction equation
[C:1]([O:4][C@H:5]1[C@H:10]([N:11]=[C:12]=[S:13])[C@@H:9]([O:14][C:15](=[O:17])[CH3:16])[C@H:8]([O:18][C:19](=[O:21])[CH3:20])[C@@H:7]([CH2:22][O:23][C:24](=[O:26])[CH3:25])[O:6]1)(=[O:3])[CH3:2].[F:27][CH2:28][CH2:29][NH2:30]>CC#N>[C:1]([O:4][C@H:5]1[C@H:10]([NH:11][C:12]([NH:30][CH2:29][CH2:28][F:27])=[S:13])[C@@H:9]([O:14][C:15](=[O:17])[CH3:16])[C@H:8]([O:18][C:19](=[O:21])[CH3:20])[C@@H:7]([CH2:22][O:23][C:24](=[O:26])[CH3:25])[O:6]1)(=[O:3])[CH3:2]

Participants

4

Reactant 2

HCID 99962-FluoroethylamineHCID 14130735(2S,3R,4R,5S,6R)-6-(acetoxymethyl)-3-isothiocyanatotetrahydro-2H-pyran-2,4,5-triyl triacetate

Product 1

HCID 86638174(2S,3R,4R,5S,6R)-6-(acetoxymethyl)-3-(3-(2-fluoroethyl)thioureido)-tetrahydro-2H-pyran-2,4,5-triyl triacetateYield 57%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of (2S,3R,4R,5S,6R)-6-(acetoxymethyl)-3-isothiocyanato-tetrahydro-2H-pyran-2,4,5-triyl triacetate (0.54 g, 1.39 mmol) in CH3CN, was added neat 2-fluoroethanamine (0.28 g, 2.79 mmol), dropwise. The reaction was stirred at room temperature until complete by TLC (3 h). The reaction was washed with a minimal amount of saturated aqueous NaHCO3 (15 mL). The aqueous layer was then extracted three times with DCM, and the organic layers were combined, dried with MgSO4, filtered and concentrated. The concentrated mixture was purified via flash column chromatography in a solvent system of EtOAc and hexanes (1:1), providing (2S,3R,4R,5S,6R)-6-(acetoxymethyl)-3-(3-(2-fluoroethyl)thioureido)-tetrahydro-2H-pyran-2,4,5-triyl triacetate (0.358 g, 57% yield). 1H NMR (500 MHz, CDCl3) δ 1.23 (t, 2H, J=7.3 Hz), 2.02 (s, 3H), 2.05 (s, 3H), 2.10 (s, 3H), 2.11 (s, 3H), 3.85-3.88 (m, 2H), 4.07-4.12 (m, 1H), 4.25 (dd, 1H, J=4.6, 12.5 Hz), 4.47-4.53 (m, 1H), 4.54-4.63 (m, 1H), 5.14 (t, 1H, J=9.7 Hz), 5.25 (t, 1H, J=5.4 Hz), 5.73 (d, 1H, J=8.6 Hz), 6.50 (d, 1H, J=9.3 Hz), 6.68 (t, 1H, J=5.4 Hz).

Workup

  1. washThe reaction was washed with a minimal amount of saturated aqueous NaHCO3 (15 mL)
  2. extractionThe aqueous layer was then extracted three times with DCM
  3. dry with materialdried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe concentrated mixture was purified via flash column chromatography in a solvent system of EtOAc and hexanes (1:1)

Sources & evidence

ORD record
ord-0bec7e36c7cf4ffc84a35405694dee6c
Source dataset
uspto-grants-2015_02
Patent number
US08962664B2

Reaction notes

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