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

HRID 1826194Notes

Reaction equation

HRID 1826194 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 was 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) was added dropwise, and the resulting mixture was stirred at −78° C. for 1 hour and at ambient temperature for 2.75 days. The reaction mixture was then quenched with saturated aqueous ammonium chloride (20 mL), diluted with water (20 mL) and the layers are separated. The aqueous phase was extracted with ethyl acetate (25 mL), and the combined organic phase was washed with water (25 mL) and saline (25 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The product mixture was 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 was stirred at −78° C. for 1 hour and at ambient temperature for 2.75 days
  2. customThe reaction mixture was then quenched with saturated aqueous ammonium chloride (20 mL)
  3. additiondiluted with water (20 mL)
  4. customthe layers are separated
  5. extractionThe aqueous phase was extracted with ethyl acetate (25 mL)
  6. washthe combined organic phase was 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 was 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-86f32f3bebc84f168b32df079cee9659
Source dataset
uspto-grants-2006_05
Patent number
US07049443B2

Reaction notes

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