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

HRID 129549Notes

Reaction equation

HRID 129549 reaction equation
COC1C=C(C=CC=1OC)[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+].C(N(CC)CC)C.C(Cl)(Cl)=[O:46]>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:46])[CH3:30])[CH:25]=[CH:24][C:23]=1[O:26][CH3:27]

Participants

6

Reactant 4

HCID 6371PhosgeneHCID 8471TriethylamineHCID 24758Sodium hydrideHCID 67780529(R)-N-(3,4-dimethoxybenzyl)-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×

Procedure

A solution of 0.8 g. of (R)-N-(3,4-dimethoxybenzyl)-N-[2-(3-chlorophenyl)-2-hydroxyeth-1-yl]-1-(3,4-dimethoxyphenyl)-prop-2-ylamine in 10 mL of toluene is added to a slurry of 64 mg. of sodium hydride (60% oil slurry) in 5 mL of toluene at room temperature. The reaction mixture is stirred for one hour, 0.11 mL of triethylamine is added, and the reaction mixture is stirred for an additional 30 minutes. A 1.93M solution of phosgene (0.9 mL) is added and the reaction mixture is stirred for one hour and quenched with 10% hydrochloric acid. Additional toluene is added and the mixture is sequentially washed with dilute hydrochloric acid, 3N sodium hydroxide, and brine, after which it is dried over magnesium sulfate and concentrated to yield (R,R)-3-[1-(3,4-dimethoxyphenyl)prop-2-yl]-5-(3-chlorophenyl)oxazolidin-2-one which is further purified by recrystallization from 1:7 ethanol:heptane to yield white crystals. Gas chromatography indicates the chemical purity is 99.9% and HPLC indicates the optical purity is 99.6%. 1H NMR (250 MHz, CDCl3) d 1.26 (d, 3H, J=6.7 Hz), 2.65-2.85 (m, 2H), 3.25 (m, 1H), 3.8-3.9 (m, 1H), 3.82 (s, 3H), 3.86 (s, 3H), 4.34 (m, 1H), 5.35 (m, 1H), 6.6-7.4 (m, 7H).

Workup

  1. customat room temperature
  2. stirringthe reaction mixture is stirred for an additional 30 minutes
  3. stirringthe reaction mixture is stirred for one hour
  4. customquenched with 10% hydrochloric acid
  5. additionAdditional toluene is added
  6. washthe mixture is sequentially washed with dilute hydrochloric acid, 3N sodium hydroxide, and brine
  7. dry with materialafter which it is dried over magnesium sulfate
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-0e3597d1e05d4d49af69c866206e152e
Source dataset
uspto-grants-1995_11
Patent number
US05468865

Reaction notes

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