Tributylphosphine oxide → (R)-[3-(3-fluorophenyl)-2-oxo-5-oxazolidinyl]methyl butyrate

HRID 2256410Notes

Reaction equation

HRID 2256410 reaction equation
[Br-].[Li+].C(P(=[O:16])(CCCC)CCCC)CCC.[C:17]([O:22][CH2:23][C@@H:24]1[O:26][CH2:25]1)(=[O:21])[CH2:18][CH2:19][CH3:20].[F:27][C:28]1[CH:29]=[C:30]([N:34]=[C:35]=O)[CH:31]=[CH:32][CH:33]=1>CC1C=CC=CC=1C>[C:17]([O:22][CH2:23][C@@H:24]1[O:26][C:25](=[O:16])[N:34]([C:30]2[CH:31]=[CH:32][CH:33]=[C:28]([F:27])[CH:29]=2)[CH2:35]1)(=[O:21])[CH2:18][CH2:19][CH3:20]

Participants

6

Reactant 4

HCID 13138Tributylphosphine oxideHCID 82050Lithium BromideHCID 1230643-Fluorophenyl isocyanateHCID 2724536(2R)-Oxiran-2-ylmethyl butanoate

Product 1

HCID 54327495(R)-[3-(3-fluorophenyl)-2-oxo-5-oxazolidinyl]methyl butyrate

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent2×

Procedure

A mixture of lithium bromide (0.181 g, 2.08 mmol), tri-n-butylphosphine oxide (0.454 g, 2.08 mmol), and dry o-xylene (10 ml) is azeotropically dried for 1 hr. After cooling below the reflux point, a mixture of (R)-glycidyl butyrate (5.000 g, 34.68 mmol) and 3-fluorophenyl isocyanate (4.755 g or 3.96 ml, 34.68 mmol) in dry o-xylene (10 ml) is added over 10 min to the hot mixture (some refining observed during the addition). When the addition is complete, the mixture is heated to reflux for 2 hr and then allowed to cool to 20°-25°. The solvent is removed under reduced pressure and the residue chromatographed over silica gel, eluting with hexane/ethyl acetate (6:1, 4:1, and then 2:1), to give the title compound, [α]25D -46.7° (c 1.0, CHCl3); IR (mineral oil mull) 1758, 1615, 1591, 1498, 1229, 1197, 1169 cm-1 ; NMR (CDCl3, 300 MHz) δ 7.44, 7.34, 7.23, 6.86, 4.88, 4.39, 4.32, 4.13, 3.82, 2.33, 1.63, 0.92; MS (m/z) 281, 193, 180, 150, 148, 137, 123, 95, 43; HRMS (m/z) 281.1068 (calc'd for C14H16FNO4 =281.1063).

Workup

  1. customis azeotropically dried for 1 hr
  2. temperatureAfter cooling below the reflux point
  3. additionis added over 10 min to the hot mixture (some refining
  4. additionobserved during the addition)
  5. additionWhen the addition
  6. temperaturethe mixture is heated
  7. temperatureto reflux for 2 hr
  8. temperatureto cool to 20°-25°
  9. customThe solvent is removed under reduced pressure
  10. customthe residue chromatographed over silica gel
  11. washeluting with hexane/ethyl acetate (6:1, 4:1

Sources & evidence

ORD record
ord-4794c49775ae4bb9abff0e3d15307f6e
Source dataset
uspto-grants-1997_08
Patent number
US05654435

Reaction notes

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