(Diethylamino)sulfur trifluoride → HCID 25168846, compound

HRID 1175312Notes

Reaction equation

HRID 1175312 reaction equation
C([O:4][C@H:5]1[C@H:10]([O:11]C(=O)C)[C@@H:9]([O:15]C(=O)C)[C@H:8]([C:19]2[CH:24]=[C:23]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([CH2:32][CH3:33])=[CH:28][CH:27]=3)[C:22]([Cl:34])=[CH:21][C:20]=2[CH2:35][CH2:36][O:37][CH2:38][CH2:39]O)[O:7][C@@H:6]1[CH2:41][O:42]C(=O)C)(=O)C.CCN(S(F)(F)[F:52])CC.O[Li].O>C(Cl)Cl.C1COCC1.CO.O>[Cl:34][C:22]1[C:23]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([CH2:32][CH3:33])=[CH:28][CH:27]=2)=[CH:24][C:19]([C@H:8]2[C@H:9]([OH:15])[C@@H:10]([OH:11])[C@H:5]([OH:4])[C@@H:6]([CH2:41][OH:42])[O:7]2)=[C:20]([CH2:35][CH2:36][O:37][CH2:38][CH2:39][F:52])[CH:21]=1

Participants

6

Reactant 3

HCID 123472(Diethylamino)sulfur trifluorideHCID 168937Lithium hydroxide, monohydrateHCID 59557723HCID 59557723, compound

Product 1

HCID 25168846HCID 25168846, compoundYield 26.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

To a cooled (−78° C.) solution of (2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(4-chloro-5-(4-ethylbenzyl)-2-(2-(2-hydroxyethoxy)ethyl)phenyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (28.7 mg, 0.044 mmol) in CH2Cl2 (1 mL) was added DAST (0.04 mL, 0.3 mmol) dropwise. After being stirred for 2.5 h at the same temperature, the reaction was quenched by addition of saturated Na2CO3. The mixture was extracted 3× with CH2Cl2, and the combined organic layers were washed 1× with brine and dried over Na2SO4. Concentration gave the crude product, which was used for the next step without further purification. To a solution of the crude product in THF:MeOH:H2O (2:3:1, 0.8 mL), was added LiOH—H2O (3.7 mg, 0.088 mmol). After being stirred overnight at room temperature, the reaction mixture was concentrated. The residue was dissolved in EtOAc, washed 1× with brine, 1× with brine containing 1% NaHSO4 and 1× with brine prior to drying over Na2SO4. Concentration gave the crude product, which was purified by preparative HPLC to yield 5.7 mg of title compound. 1H-NMR (CD3OD, 300 MHz) δ 7.38 (s, 1H), 7.26 (s, 1H), 7.08 (s, 4H), 4.59-4.56 (m, 1H), 4.46-4.40 (m, 2H), 4.05 (d, J=15.1 Hz, 1H), 3.99 (d, J=15.1 Hz, 1H), 3.84 (d, J=12.0 Hz, 1H), 3.75-3.61 (m, 5H), 3.48-3.36 (m, 4H), 3.13-3.03 (m, 1H), 2.96-2.87 (m, 1H), 2.57 (q, J=7.6 Hz, 2H), 1.18 (t, J=7.6 Hz, 3H); MS ESI (m/z) 483 (M+1)+, calc. 482.

Workup

  1. customthe reaction was quenched by addition of saturated Na2CO3
  2. extractionThe mixture was extracted 3× with CH2Cl2
  3. washthe combined organic layers were washed 1× with brine
  4. dry with materialdried over Na2SO4
  5. concentrationConcentration
  6. customgave the crude product, which
  7. customwas used for the next step without further purification
  8. stirringAfter being stirred overnight at room temperature
  9. concentrationthe reaction mixture was concentrated
  10. dissolutionThe residue was dissolved in EtOAc
  11. washwashed 1× with brine, 1× with brine containing 1% NaHSO4 and 1× with brine
  12. dry with materialto drying over Na2SO4
  13. concentrationConcentration
  14. customgave the crude product, which
  15. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-0e46e31fd72443a488e1d98cec7d2112
Source dataset
uspto-grants-2010_11
Patent number
US07838498B2

Reaction notes

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