Potassium Phosphate, Dibasic → (S)-(-)-N-[[3-[4-[1-(5-Methyl-1,3,4-thiadiazol-2-yl)-3,6-dihydro-2H-pyridin-4-yl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide

HRID 1276463Notes

Reaction equation

HRID 1276463 reaction equation
[O:1]=[C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[C:9]([F:19])[CH:8]=2)[CH2:5][C@H:4]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:3]1.Br[C:26]1[S:27][C:28]([CH3:31])=[N:29][N:30]=1.P([O-])([O-])(O)=O.[K+].[K+]>CS(C)=O.O>[CH3:31][C:28]1[S:27][C:26]([N:16]2[CH2:15][CH:14]=[C:13]([C:10]3[CH:11]=[CH:12][C:7]([N:6]4[CH2:5][C@H:4]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:3][C:2]4=[O:1])=[CH:8][C:9]=3[F:19])[CH2:18][CH2:17]2)=[N:30][N:29]=1

Participants

6

Reactant 3

HCID 24450Potassium Phosphate, DibasicHCID 71719042-Bromo-5-methyl-1,3,4-thiadiazoleHCID 15887422(S)-(-)-N-[[2-Oxo-3-[4-(4-piperidinyl)-3-fluorophenyl]-5-oxazolidinyl]methyl]acetamide

Product 1

HCID 54020133(S)-(-)-N-[[3-[4-[1-(5-Methyl-1,3,4-thiadiazol-2-yl)-3,6-dihydro-2H-pyridin-4-yl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (S)-(-)-N-[[2-oxo-3-[4-(4-piperidinyl)-3-fluorophenyl]-5-oxazolidinyl]methyl]acetamide (EXAMPLE 20, 550 mg), 2-bromo-5-methyl-1,3,4-thiadiazole (EXAMPLE 87, Step 1, 323 mg) and potassium hydrogenphosphate (571 mg) in dimethyl sulfoxide (16 mL) is stirred under N2 at 100° C. for 2 hrs, cooled to ambient temperature, diluted with water (20 mL) and extracted with methylene chloride (3×20 mL). The combined organic phase is washed with water (20 mL) and saline (10 mL), dried over anhydrous sodium sulfate and concentrated to give the crude product which is then chromatographed on silica gel (230-400 mesh, 45 g), eluting with a gradient of methanol/methylene chloride (2/98-3/97). Pooling and concentration of those fractions with an Rf =0.44 by TLC (methanol/chloroform, 10/90) gives the title compound, mp 193-195° C.

Workup

  1. temperaturecooled to ambient temperature
  2. extractionextracted with methylene chloride (3×20 mL)
  3. washThe combined organic phase is washed with water (20 mL) and saline (10 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customto give the crude product which
  7. customis then chromatographed on silica gel (230-400 mesh, 45 g)
  8. washeluting with a gradient of methanol/methylene chloride (2/98-3/97)

Sources & evidence

ORD record
ord-14d48f94fdf544309709f5333737cc34
Source dataset
uspto-grants-2000_12
Patent number
US06166056

Reaction notes

Loading…