(2R)-Oxiran-2-ylmethyl butanoate → (R)-(-)-3,6-Dihydro-4-[4-[5-(hydroxymethyl)-2-oxo-3-oxazolidinyl]phenyl]-1(2 H)-pyridinecarboxylic acid phenylmethyl ester

HRID 1004804Notes

Reaction equation

HRID 1004804 reaction equation
[C:1]1([CH2:7][O:8][C:9]([N:11]2[CH2:16][CH:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([NH:23][C:24](OCC4C=CC=CC=4)=O)=[CH:19][CH:18]=3)[CH2:13][CH2:12]2)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Li])CCC.[C:39]([O:44][CH2:45][C@@H:46]1[O:48]C1)(=[O:43])CCC>O1CCCC1>[C:1]1([CH2:7][O:8][C:9]([N:11]2[CH2:12][CH:13]=[C:14]([C:17]3[CH:18]=[CH:19][C:20]([N:23]4[CH2:24][C@H:45]([CH2:46][OH:48])[O:44][C:39]4=[O:43])=[CH:21][CH:22]=3)[CH2:15][CH2:16]2)=[O:10])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 2724536(2R)-Oxiran-2-ylmethyl butanoateHCID 542717983,6-Dihydro-4-[4-[[(phenylmethoxy)carbonyl]amino]phenyl]-1(2H)-pyridinecarboxylic acid phenylmethyl esterHCID 178418339Butyllithium

Product 1

HCID 54330421(R)-(-)-3,6-Dihydro-4-[4-[5-(hydroxymethyl)-2-oxo-3-oxazolidinyl]phenyl]-1(2 H)-pyridinecarboxylic acid phenylmethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 3,6-dihydro-4-[4-[[(phenylmethoxy)carbonyl]amino]phenyl]-1(2H)-pyridinecarboxylic acid phenylmethyl ester (EXAMPLE 17, Step 2, 0.500 g) in dry tetrahydrofuran (5.7 mL) at -78° C. under N2 is treated with n-butyllithium (0.73 mL, 1.6M in hexanes) dropwise over five minutes. The resulting mixture is stirred at -78° C. for 45 minutes and is then treated with (R)-(-)-glycidyl butyrate dropwise. The resulting solution is allowed to warm to ambient temperature over approximately 45 minutes and is stirred for an additional 20 hours, after which the reaction is quenched with saturated aqueous ammonium chloride (10 mL), diluted with water (20 mL) and extracted with ethyl acetate (2×15 mL). The combined organic phase is washed with saline (10 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the crude product which is chromatographed on silica gel (230-400 mesh, 40 g), eluting with methanol/methylene chloride (1/99). Pooling and concentration of those fractions with an Rf =0.37 by TLC (methanol/chloroform, 5/95) gives the title compound, mp 131.5-133.5° C.

Workup

  1. temperatureto warm to ambient temperature over approximately 45 minutes
  2. stirringis stirred for an additional 20 hours
  3. customafter which the reaction is quenched with saturated aqueous ammonium chloride (10 mL)
  4. additiondiluted with water (20 mL)
  5. extractionextracted with ethyl acetate (2×15 mL)
  6. washThe combined organic phase is washed with saline (10 mL)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customto give the crude product which
  10. customis chromatographed on silica gel (230-400 mesh, 40 g)
  11. washeluting with methanol/methylene chloride (1/99)

Sources & evidence

ORD record
ord-4f5b8d0e3c654fc7911f1b3f9099cfac
Source dataset
uspto-grants-2000_04
Patent number
US06051716

Reaction notes

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