Methyl iodide → HCID 86691701, compound

HRID 1022470Notes

Reaction equation

HRID 1022470 reaction equation
[C:1]([O:4][C@H: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]([C:19]2[CH:24]=[CH:23][C:22]([CH:25]3[CH2:27][CH2:26]3)=[C:21]([CH2:28][C:29]3[CH:38]=[CH:37][C:32]4[O:33][CH2:34][CH2:35][O:36][C:31]=4[CH:30]=3)[CH:20]=2)[O:7][CH:6]1OC(=O)C)(=[O:3])[CH3:2].N[C:44](N)=[S:45].FC(F)(F)S(O[Si](C)(C)C)(=O)=O.CI.C(N(C(C)C)CC)(C)C>O1CCOCC1.C(OCC)(=O)C>[C:12]([O:11][C@@H:10]1[C@@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@H:8]([C:19]2[CH:24]=[CH:23][C:22]([CH:25]3[CH2:27][CH2:26]3)=[C:21]([CH2:28][C:29]3[CH:38]=[CH:37][C:32]4[O:33][CH2:34][CH2:35][O:36][C:31]=4[CH:30]=3)[CH:20]=2)[O:7][CH:6]([S:45][CH3:44])[C@H:5]1[O:4][C:1](=[O:3])[CH3:2])(=[O:14])[CH3:13]

Participants

8

Reactant 5

HCID 6328Methyl iodideHCID 65367Trimethylsilyl triflateHCID 81531DiisopropylethylamineHCID 2723790ThioureaHCID 86691700HCID 86691700, compound

Product 1

HCID 86691701HCID 86691701, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Step-X: To a stirred solution of acetic acid (3S,4R,5S,6S)-3,4,5-triacetoxy-6-[4-cyclopropyl-3-(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-phenyl]-tetrahydro-pyran-2-yl ester (1.9 g, 3.3 mmol) in dioxane (8 ml) was added thiourea followed by trimethylsilyl trifluoromethane sulfonate (0.88 ml, 4.8 mmol). The reaction mixture was heated to 80° C. for 3 h. Reaction mixture was cooled to room temperature and added methyl iodide (0.52 ml, 8.1 mmol) followed by diisopropylethyl amine (2.79 ml, 16.2 mmol) and stirred for additional 3 h. Reaction mixture was diluted with ethyl acetate (40 ml) and washed with water (40 ml). The organic layer was concentrated. The resulting residue was taken in methanol (10 ml) and heated to 60° C. for 2 h, then cooled to 0° C. and stirred for additional 1 h. The resulting solid was filtered and washed with methanol to give 750 mg of acetic acid (3S,4R,5S,6S)-4,5-diacetoxy-6-[4-cyclopropyl-3-(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-phenyl]-2-methylsulfanyl-tetrahydro-pyran-3-yl ester. 1H NMR (400 MHz, DMSO-d6): δ 0.55-0.59 (m, 2H), 0.85 (d, J=8.8 Hz, 2H), 1.70 (s, 3H), 1.82-1.89 (m, 1H), 1.93 (s, 3H), 2.03 (s, 3H), 2.08 (s, 3H), 3.95 (d, J=15.2 Hz, 1H), 4.02 (d, J=16.8 Hz, 1H), 4.00 (s, 4H), 4.65 (d, J=10.0 Hz, 1H), 4.87 (d, J=10.0 Hz, 1H), 5.03-5.12 (m, 2H), 5.34 (t, J=10.0 Hz, 1H), 6.58-6.60 (m, 2H), 6.73 (d, J=7.6 Hz, 1H), 6.91 (d, J=8.0 Hz, 1H), 7.04 (d, J=8.0 Hz, 1H), 7.15 (d, J=8.0 Hz, 1H). MS (ES) m/z 588.3 (M+18).

Workup

  1. customReaction mixture
  2. temperaturewas cooled to room temperature
  3. customReaction mixture
  4. washwashed with water (40 ml)
  5. concentrationThe organic layer was concentrated
  6. temperatureheated to 60° C. for 2 h
  7. temperaturecooled to 0° C.
  8. stirringstirred for additional 1 h
  9. filtrationThe resulting solid was filtered
  10. washwashed with methanol

Sources & evidence

ORD record
ord-92054831ef9b43319307e893b037e570
Source dataset
uspto-grants-2014_05
Patent number
US08722633B2

Reaction notes

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