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

HRID 1396286Notes

Reaction equation

HRID 1396286 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.[CH2:27]([O:34][CH2:35][CH2:36][NH2:37])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.FC(F)(F)C(O)=O.C([O-])(O)=O.[Na+]>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:37][CH2:36][CH2:35][O:34][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[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 516892Sodium BicarbonateHCID 5338682-(Benzyloxy)ethanamineHCID 14130735(2S,3R,4R,5S,6R)-6-(acetoxymethyl)-3-isothiocyanatotetrahydro-2H-pyran-2,4,5-triyl triacetate

Product 1

HCID 86701121[(3aR,5R,6S,7R,7aR)-6,7-diacetyloxy-2-(2-phenylmethoxyethylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]thiazol-5-yl]methyl acetateYield 81.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (2S,3R,4R,5S,6R)-6-(acetoxymethyl)-3-isothiocyanato-tetrahydro-2H-pyran-2,4,5-triyl triacetate (9.8 g, 25 mmol) in dichloromethane (100 mL) was added 128 (4 g, 26 mmol) at 0° C. After stirred for 2 hours, trifluoroacetic acid (15.4 g, 159 mmol) was added. The resulting solution was stirred for 12 hours at room temperature, then quenched with ice-water (200 mL) and neutralized by the addition of NaHCO3 (26 g, 318 mmol). The organic layer was separated and the aqueous layer was extracted with dichloromethane (3×100 mL). The combined organic layer was washed with brine (2×100 mL), dried over anhydrous sodium sulfate, and concentrated under vacuum to give a residue, which was purified by silica gel column, eluted with 10%-50% ethyl acetate in petroleum ether to afford 129 as a white syrup (9.8 g, 77%). (ES, m/z) [M+H]+ 481.0; 1H NMR (300 MHz, CDCl3) δ 7.31-7.38 (m, 5H), 6.24 (d, J=6.3 Hz, 1H), 5.41-5.43 (m, 1H), 4.94-4.98 (m, 1H), 4.55 (s, 2H), 4.34-4.37 (m, 1H), 4.14-4.16 (m, 3H), 3.83-3.87 (m, 1H), 3.64 (t, J=5.4 Hz, 2H), 3.53 (t, J=5.1 Hz, 2H), 2.12 (s, 3H), 2.10 (s, 3H), 2.09 (s, 3H).

Workup

  1. stirringThe resulting solution was stirred for 12 hours at room temperature
  2. customquenched with ice-water (200 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with dichloromethane (3×100 mL)
  5. washThe combined organic layer was washed with brine (2×100 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customto give a residue, which
  9. customwas purified by silica gel column
  10. washeluted with 10%-50% ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-fd8f3a79bef64dfaa633c397be147fd5
Source dataset
uspto-grants-2014_12
Patent number
US08901087B2

Reaction notes

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