Methyl iodide → HCID 90177023, compound

HRID 1499304Notes

Reaction equation

HRID 1499304 reaction equation
C(O[CH:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([O:19][C:20](=[O:22])[CH3:21])[C@H:7]([C:23]2[CH:28]=[CH:27][C:26]([CH3:29])=[C:25]([CH2:30][C:31]3[CH:36]=[CH:35][C:34]([O:37]CC4C=CC=CC=4)=[CH:33][CH:32]=3)[CH:24]=2)[O:6]1)(=O)C.N[C:46](N)=[S:47].[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C.CI.CCN(C(C)C)C(C)C>C1COCC1.O1CCOCC1.[Pd]>[C:20]([O:19][C@@H:8]1[C@@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@@H:5]([S:47][CH3:46])[O:6][C@H:7]1[C:23]1[CH:28]=[CH:27][C:26]([CH3:29])=[C:25]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([OH:37])=[CH:33][CH:32]=2)[CH:24]=1)(=[O:22])[CH3:21]

Participants

9

Reactant 5

HCID 6328Methyl iodideHCID 65367Trimethylsilyl triflateHCID 81531DiisopropylethylamineHCID 2723790ThioureaHCID 90177011HCID 90177011, compound

Product 1

HCID 90177023HCID 90177023, compoundYield 88%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

(3S,4R,5S,6S)-6-(3-(4-(benzyloxy)benzyl)-4-methylphenyl)tetrahydro-2H-pyran-2,3,4,5-tetrayl tetraacetate (36, 5.29 g, 8.8 mmol) was hydrogenated over 10% Pd/C (50% wet) (0.93 g, 0.44 mmol) in THF (44 mL) under hydrogen at atmospheric pressure for 1 hour. The reaction was filtered through celite, concentrated under vacuum, azeotroped twice with toluene, and placed on the high vacuum to dry thoroughly. The resulting phenol was carried to the next step without further purification. It was combined with thiourea (2.01 g, 26 mmol) and dissolved in dioxane (44 mL). TMSOTf (4.8 mL, 26 mmol) was added. The reaction was heated at 80° C. for 3 hours and then cooled to room temperature. Methyl iodide (2.2 mL, 35 mmol) was added, followed by DIPEA (12 mL, 70 mmol). The reaction was stirred overnight, then quenched with saturated aqueous NaHSO4 (150 mL), stirred vigorously for 2 hours, diluted with EtOAc, washed with H2O and brine (with back extraction), dried over MgSO4, filtered, and concentrated under vacuum. The residue was purified by silica gel chromatography (gradient 0-50% EtOAc/hexanes) to give 3.88 g (88% yield) of the product 37 as a white foam. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.10-7.19 (m, 2H), 7.03 (s, 1 H), 6.94 (d, J=8.6 Hz, 2 H), 6.68-6.77 (m, 2 H), 5.33 (t, J=9.3 Hz, 1 H), 5.21 (t, J=9.6 Hz, 1 H), 5.12 (t, J=9.6 Hz, 1H), 4.59 (s, 1 H), 4.52 (d, J=9.9 Hz, 1 H), 4.38 (d, J=9.9 Hz, 1H), 3.82-3.96 (m, 2 H), 2.21 (s, 3 H), 2.18 (s, 3 H), 2.10 (s, 3 H), 2.01 (s, 3 H), 1.75 (s, 3 H); MS (ES+) [M+NH4]+=520.

Workup

  1. filtrationThe reaction was filtered through celite
  2. concentrationconcentrated under vacuum
  3. customazeotroped twice with toluene
  4. customto dry thoroughly
  5. customThe resulting phenol was carried to the next step without further purification
  6. temperaturecooled to room temperature
  7. customquenched with saturated aqueous NaHSO4 (150 mL)
  8. stirringstirred vigorously for 2 hours
  9. additiondiluted with EtOAc
  10. washwashed with H2O and brine (with back extraction)
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated under vacuum
  14. customThe residue was purified by silica gel chromatography (gradient 0-50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-a65f97dddf23497dbf46cbe0a636288c
Source dataset
uspto-grants-2015_12
Patent number
US09200025B2

Reaction notes

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