Methyl iodide → HCID 86600447, compound

HRID 2103383Notes

Reaction equation

HRID 2103383 reaction equation
[Si:1]([O:8][C@H:9]1[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C@H:11]([C:21]([O:23][CH3:24])=[O:22])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:25][Si]([N-][Si](C)(C)C)(C)C.[Li+].IC>C1COCC1>[Si:1]([O:8][C@H:9]1[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:15])[C:11]([CH3:25])([C:21]([O:23][CH3:24])=[O:22])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 10618477(2S,4R)-1-tert-Butyl 2-methyl 4-((tert-butyldimethylsilyl)oxy)pyrrolidine-1,2-dicarboxylate

Product 1

HCID 86600447HCID 86600447, compoundYield 50.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1-tert-butyl 2-methyl (2S,4R)-4-{[tert-butyl(dimethyl)silyl]oxy}pyrrolidine-1,2-dicarboxylate (5.11 g, 14.2 mmol) in dry THF (60 mL) at −78° C. was dropwise added lithium bistrimethylsilylamide (17.0 mL, 17.0 mmol, 1.0 M in THF). After being stirred for 30 minutes, iodomethane (1.77 mL, 28.4 mmol) was then added. The mixture was stirred at −78° C. for one hour, warmed to 0° C. for one hour and finally quenched with NaHCO3/H2O. The resulting mixture was extracted twice with ethyl acetate. The combined extracts were dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel eluting with hexane to 5% ethyl acetate/hexane to provide 2.66 g (50%) of a mixture of product isomers as a colorless oil. LC/MS (M-Boc+H)+ m/z=274.1. 1H NMR (CDCl3) δ 4.38 (m, 1H), 3.71 (m, 4H), 3.36 (m, 1H), 1.84-2.35 (m, 2H), 1.61 (m, 3H), 1.44 (m, 9H), 0.88 (m, 9H), 0.07 (m, 6H).

Workup

  1. customat −78° C.
  2. stirringThe mixture was stirred at −78° C. for one hour
  3. customfinally quenched with NaHCO3/H2O
  4. extractionThe resulting mixture was extracted twice with ethyl acetate
  5. dry with materialThe combined extracts were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was chromatographed on silica gel eluting with hexane to 5% ethyl acetate/hexane

Sources & evidence

ORD record
ord-45745532a9684fd292cd689e0fb5cd78
Source dataset
uspto-grants-2009_08
Patent number
US07576089B2

Reaction notes

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