(2R)-Oxiran-2-ylmethyl butanoate → Compound 3

HRID 723825Notes

Reaction equation

HRID 723825 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:9][C:10](=O)OCC(C)C)[CH:5]=[CH:6][C:7]=1[I:8].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[C:27]([O:32][CH2:33][C@@H:34]1[O:36]C1)(=[O:31])CCC>O1CCCC1>[F:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:10][C@H:33]([CH2:34][OH:36])[O:32][C:27]2=[O:31])[CH:5]=[CH:6][C:7]=1[I:8]

Participants

5

Reactant 3

HCID 2724536(2R)-Oxiran-2-ylmethyl butanoateHCID 2733832Lithium HexamethyldisilazideHCID 15908282Isobutyl 3-fluoro-4-iodophenylcarbamate

Product 1

HCID 20788885Compound 3

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of isobutyl 3-fluoro-4-iodophenylcarbamate (Org. Process Res. Dev. 2001, 5(1), 80–83, 5.00 g, 14.83 mmol) in dry tetrahydrofuran (59 mL) at −78° C. under nitrogen is treated with lithium hexamethyldisilazide (1.0M in tetrahydrofuran, 15.6 mL, 15.57 mmol) dropwise and stirred at −78° C. for 45 minutes. Then, (R)-glycidyl butyrate (2.21 mL, 15.57 mmol) is added dropwise, and the resulting mixture is stirred at −78° C. for 1 h and at ambient temperature for 2.75 days. The reaction mixture is then quenched with saturated aqueous ammonium chloride (20 mL), diluted with water (20 mL) and the layers are separated. The aqueous phase is extracted with ethyl acetate (25 mL), and the combined organic phase is washed with water (25 mL) and saline (25 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The product mixture is then chromatographed on a Flash 40M silica gel (90 g, 32–63 μm) cartridge, eluting with a gradient of methanol/methylene chloride (1/99–2/98), and those fractions with an Rf=0.25 by TLC (methanol/chloroform, 5/95) are pooled and concentrated to give the title compound, mp 116–117° C.; MS (ESI+) for C10H9FINO3 m/z 338 (M+H)+; [α]25D=−41 (c 0.98, DMSO).

Workup

  1. stirringthe resulting mixture is stirred at −78° C. for 1 h and at ambient temperature for 2.75 days
  2. customThe reaction mixture is then quenched with saturated aqueous ammonium chloride (20 mL)
  3. additiondiluted with water (20 mL)
  4. customthe layers are separated
  5. extractionThe aqueous phase is extracted with ethyl acetate (25 mL)
  6. washthe combined organic phase is washed with water (25 mL) and saline (25 mL)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe product mixture is then chromatographed on a Flash 40M silica gel (90 g, 32–63 μm) cartridge
  10. washeluting with a gradient of methanol/methylene chloride (1/99–2/98)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-63e89964532840dc987f5d49ab4b8b42
Source dataset
uspto-grants-2006_11
Patent number
US07141588B2

Reaction notes

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