Trifluoroacetic acid → [(3aR,5R,6S,7R,7aR)-6,7-diacetyloxy-2-(2-fluoroethylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]thiazol-5-yl]methyl acetate

HRID 1396254Notes

Reaction equation

HRID 1396254 reaction equation
C(O[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)C.Cl.[F:28][CH2:29][CH2:30][NH2:31].C(N(CC)CC)C.FC(F)(F)C(O)=O>ClCCl>[C:19]([O:18][C@@H:8]1[C@@H:7]([CH2:22][O:23][C:24](=[O:26])[CH3:25])[O:6][C@H:5]2[C@H:10]([N:11]=[C:12]([NH:31][CH2:30][CH2:29][F:28])[S:13]2)[C@H:9]1[O:14][C:15](=[O:17])[CH3:16])(=[O:21])[CH3:20]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 9995Ethanamine, 2-fluoro-, hydrochlorideHCID 14130735(2S,3R,4R,5S,6R)-6-(acetoxymethyl)-3-isothiocyanatotetrahydro-2H-pyran-2,4,5-triyl triacetate

Product 1

HCID 59153312[(3aR,5R,6S,7R,7aR)-6,7-diacetyloxy-2-(2-fluoroethylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]thiazol-5-yl]methyl acetateYield 79.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of (2S,3R,4R,5S,6R)-6-(acetoxymethyl)-3-isothiocyanato-tetrahydro-2H-pyran-2,4,5-triyl triacetate (30 g, 77 mmol) in dichloromethane (100 mL) was added 2-fluoroethylamine hydrochloride (8.4 g, 84 mmol) and triethylamine (11.7 mL, 115 mmol). The resulting solution was stirred for 1 hour at room temperature, and then condensed to give a light yellow foam, which was dissolved into dichloromethane (100 mL) and treated with 2,2,2-trifluoroacetic acid (75.6 g, 663 mmol) overnight at room temperature. The reaction mixture was quenched by saturated aqueous sodium carbonate (500 mL), washed with sodium chloride (3×50 mL), dried over anhydrous magnesium sulfate, and concentrated under vacuum to give a residue, which was purified by a silica gel column, eluting with 50% ethyl acetate in petroleum ether to provide compound 66 as a light yellow oil (24 g, 70%). (ES, m/z) [M+H]+ 393.0; 1H NMR (300 MHz, CDCl3) δ 6.27-6.29 (d, J=6.60 Hz, 1H), 5.42-5.44 (1, J=2.7 Hz, 1H), 4.95-4.99 (dd, J=1.8 Hz, 9.5 Hz, 1H), 4.70-4.73 (m, 1H), 4.54-4.65 (m, 1H), 4.37-4.39 (t, J=0.9 Hz, 1H), 4.16-4.17 (m, 2H), 3.81-3.87 (m, 1H), 3.56-3.71 (m, 2H), 2.09 (s, 3H), 2.11 (s, 3H), 2.14 (s, 3H),

Workup

  1. customcondensed
  2. customto give a light yellow foam, which
  3. customThe reaction mixture was quenched by saturated aqueous sodium carbonate (500 mL)
  4. washwashed with sodium chloride (3×50 mL)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under vacuum
  7. customto give a residue, which
  8. customwas purified by a silica gel column
  9. washeluting with 50% ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-7764b0d614ea45879c7383db11676540
Source dataset
uspto-grants-2014_12
Patent number
US08901087B2

Reaction notes

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