1-Chloroethyl chloroformate → 2-(S)-(3,5-Dichlorobenzyloxy)-3-(S)-phenylmorpholine

HRID 363124Notes

Reaction equation

HRID 363124 reaction equation
C([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([O:14][CH2:15][C:16]2[CH:21]=[C:20]([Cl:22])[CH:19]=[C:18]([Cl:23])[CH:17]=2)[C@@H:9]1[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)C1C=CC=CC=1.ClC(OC(Cl)C)=O>ClCCCl>[Cl:23][C:18]1[CH:17]=[C:16]([CH:21]=[C:20]([Cl:22])[CH:19]=1)[CH2:15][O:14][C@H:10]1[O:11][CH2:12][CH2:13][NH:8][C@H:9]1[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 228607764-benzyl-2-(S)-(3,5-dichlorobenzyloxy)-3-(S)-phenylmorpholine

Product 1

HCID 228607442-(S)-(3,5-Dichlorobenzyloxy)-3-(S)-phenylmorpholineYield 20%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
110 °C

Procedure

A solution of 0.33 g (0.77 mmole) of 4-benzyl-2-(S)-(3,5-dichlorobenzyloxy)-3-(S)-phenylmorpholine (from Example 44, Step B) and 0.22 g (1.54 mmole) of 1-chloroethyl chloroformate in 4.5 mL of 1,2-dichloroethane was placed in a pressure vial which was lowered into an oil bath which was heated to 110° C. After stirring for 60 hr the solution was cooled and concentrated in vacuo. The residue was dissolved in 7 mL of methanol and the resulting solution was heated at reflux for 30 min. The mixture was cooled and treated with several drops of concentrated aqueous ammonia and the solution was concentrated. The residue was partly purified by flash chromatography on 67 g of silica eluting with 1.5 L of 100:1 methylene chloride: methanol, and the rich cuts were purified by flash chromatography on 32 g of silica eluting with 50:50 hexanes: ethyl acetate and then 50:50:5 hexanes:ethyl acetate:methanol to give 0.051 g (20%) of an oil, which by 1H NMR was pure cis morpholine.

Workup

  1. customwas lowered into an oil bath
  2. temperaturewas cooled
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in 7 mL of methanol
  5. temperaturethe resulting solution was heated
  6. temperatureat reflux for 30 min
  7. temperatureThe mixture was cooled
  8. additiontreated with several drops of concentrated aqueous ammonia
  9. concentrationthe solution was concentrated
  10. customThe residue was partly purified by flash chromatography on 67 g of silica eluting with 1.5 L of 100:1 methylene chloride
  11. custommethanol, and the rich cuts were purified by flash chromatography on 32 g of silica eluting with 50:50 hexanes

Sources & evidence

ORD record
ord-dec8821dc6c8435391530206980b5dd8
Source dataset
uspto-grants-1999_02
Patent number
US05872116

Reaction notes

Loading…