Methyl iodide → HCID 11010979, compound

HRID 1367671Notes

Reaction equation

HRID 1367671 reaction equation
C[Si](C)(C)N[Si](C)(C)C.[Na].[CH:11]([C@H:14]1[CH2:18][O:17][C:16](=[O:19])[N:15]1[C:20](=[O:28])[CH2:21][CH2:22][CH2:23][CH2:24][C:25]([CH3:27])=[CH2:26])([CH3:13])[CH3:12].I[CH3:30]>C1COCC1>[CH3:30][C@@H:21]([CH2:22][CH2:23][CH2:24][C:25]([CH3:27])=[CH2:26])[C:20]([N:15]1[C@@H:14]([CH:11]([CH3:13])[CH3:12])[CH2:18][O:17][C:16]1=[O:19])=[O:28]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 18393304HCID 18393304, compoundHCID 45051731Sodium hexamethyidisilazane

Product 1

HCID 11010979HCID 11010979, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

As reported by Schinzer et al.104 Sodium hexamethyldisilazane (13 ml of 1.0 M in THF, 13 mmol, 1.1 equiv) was added dropwise to a solution of imide 73 (3.0 g, 11.9 mmol, 1 equiv) in THF (15 ml) at −78° C. The reaction mixture was stirred for 30 min and a solution of iodomethane (3.74 ml, 60 mmol, 5 equiv) in THF (2 ml) was added dropwise. After stirring for 10 h at −78° C., the reaction was quenched with saturated aqueous ammonium chloride (10 ml), and extracted with ether (4×50 ml). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give crude product 74 (12:1 ratio of diastereomers by 1H NMR). Purification by flash column chromatography (10% EtOAc/hexanes) afforded compound 74 (2.69 g, 85%) as a colorless oil: [α]22D=+ 87.2 (c=0.5, CHCl3); TLC Rf=0.47 (silica gel, 25% EtOAc/hexanes); 1H NMR (600 MHz, CDCl3) δ 4.674 (s, 1H), 4.642 (s, 1H), 4.45-4.42 (m, 1H), 4.265-4.23 (t, 2J=9 Hz, 1H), 4.2-4.17 (dd, 2J=9.6 Hz, 3J=3 Hz, 1H), 3.75-3.69 (m, 1H), 2.36-2.29 (m, 1H), 2.01-1.97 (t, 2J=7.2 Hz, 2H), 1.68 (s, 3H), 1.57-1.30 (m, 4H), 1.195-1.183 (d, 3J=7.2 Hz, 3H), 0.9-0.888 (d, 3J=7.2 Hz, 3H), 0.861-0.85 (d, 3J=6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 177.338, 153.886, 145.779, 110.214, 63.414, 58.628, 37.903, 37.866, 32.833, 28.632, 25.381, 22.538, 18.165, 18.132, 14.901.

Workup

  1. stirringAfter stirring for 10 h at −78° C.
  2. customthe reaction was quenched with saturated aqueous ammonium chloride (10 ml)
  3. extractionextracted with ether (4×50 ml)
  4. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give crude product 74 (12:1 ratio of diastereomers by 1H NMR)
  8. customPurification by flash column chromatography (10% EtOAc/hexanes)

Sources & evidence

ORD record
ord-9171714717dc42009759729d660bd985
Source dataset
uspto-grants-2011_02
Patent number
US07893268B2

Reaction notes

Loading…