Phosgene → (R,R)-3-[1-(3,4-dimethoxyphenyl)prop-2-yl]-5-(3-chlorophenyl)oxazolidin-2-one

HRID 129551Notes

Reaction equation

HRID 129551 reaction equation
COC1C=C(C=CC=1OCCCC)[CH2:6][N:7]([C@H:18]([CH3:30])[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[CH:21]=1)[CH2:8][CH:9]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=1)[OH:10].[H-].[Na+].N1C(C)=CC=CC=1C.C(Cl)(Cl)=[O:50]>C1(C)C=CC=CC=1>[CH3:29][O:28][C:22]1[CH:21]=[C:20]([CH2:19][C@H:18]([N:7]2[CH2:8][C@@H:9]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=3)[O:10][C:6]2=[O:50])[CH3:30])[CH:25]=[CH:24][C:23]=1[O:26][CH3:27]

Participants

6

Reactant 4

HCID 6371PhosgeneHCID 79372,6-LutidineHCID 24758Sodium hydrideHCID 67781069(R)-N-(3-methoxy-4-n-butoxybenzyl)-N-[2-(3-chlorophenyl)-2-hydroxyeth-1-yl]-1-(3,4-dimethoxyphenyl)-prop-2-ylamine

Product 1

HCID 9885973(R,R)-3-[1-(3,4-dimethoxyphenyl)prop-2-yl]-5-(3-chlorophenyl)oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 5.0 g. of (R)-N-(3-methoxy-4-n-butoxybenzyl)-N-[2-(3-chlorophenyl)-2-hydroxyeth-1-yl]-1-(3,4-dimethoxyphenyl)-prop-2-ylamine (obtained in Example 2) in 45 mL of toluene is added to 406 mg. of sodium hydride at room temperature. The mixture is stirred for one hour, 1.29 mL of 2,6-lutidine are added, and stirring is continued for 30 minutes. The reaction mixture then is added with stirring to 5.74 mL of a 20% solution of phosgene in toluene which has been cooled to 0° C. Excess phosgene is destroyed with 3N sodium hydroxide and the reaction mixture diluted with toluene, washed sequentially with 3N sodium hydroxide and brine, dried over magnesium sulfate, and evaporated to yield (R,R)-3-[1-(3,4-dimethoxyphenyl)prop-2-yl]-5-(3-chlorophenyl)oxazolidin-2-one. This is further purified by stirring in heptane at 55° C. for 15 minutes, filtering, washing with additional heptane, and recrystallization from 5:4 ethyl acetate:heptane to yield white crystals. Gas chromatography indicates the chemical purity is 99.3% and HPLC indicates the de is 99.6%.

Workup

  1. customat room temperature
  2. stirringstirring
  3. waitis continued for 30 minutes
  4. additionThe reaction mixture then is added
  5. customExcess phosgene is destroyed with 3N sodium hydroxide
  6. additionthe reaction mixture diluted with toluene
  7. washwashed sequentially with 3N sodium hydroxide and brine
  8. dry with materialdried over magnesium sulfate
  9. customevaporated

Sources & evidence

ORD record
ord-b1c5bbda7fa0481cae69c6e15f67a0aa
Source dataset
uspto-grants-1995_11
Patent number
US05468865

Reaction notes

Loading…