Ethyl Acetate → HCID 57364135, compound

HRID 880232Notes

Reaction equation

HRID 880232 reaction equation
C([N:8]1[CH2:13][CH2:12][O:11][C@@H:10]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[CH2:9]1)C1C=CC=CC=1.[Cl:21]C(OC(Cl)C)=O.CCOC(C)=O.CCOC(C)=O.CO>ClCCCl.CO>[ClH:21].[F:20][C:17]1[CH:16]=[CH:15][C:14]([C@@H:10]2[O:11][CH2:12][CH2:13][NH:8][CH2:9]2)=[CH:19][CH:18]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 5213051-Chloroethyl chloroformateHCID 12002488(S)-4-Benzyl-2-(4-fluorophenyl)morpholineHCID 21584119Ethylacetate methanol

Product 1

HCID 57364135HCID 57364135, compoundYield 39.4%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

Dissolve (2S)-4-benzyl-2-(4-fluorophenyl)morpholine (948 g, 3.5 mol) in 1,2-dichloroethane (17 L). Heat the mixture to 70° C. and add 1-chloroethyl chloroformate (1500 g, 10.5 mol) drop-wise while heating. Stir the mixture at 70° C. for 3 h and then concentrate the mixture to give a residue. Dissolve the residue in MeOH (10 L) and heat to 70° C. while stirring for 1 h. Concentrate the solution under reduced pressure to give a residue. Slurry the residue with EtOAc (5 L); filter; and wash the solid with EtOAc (1 L) to provide an off white solid. Slurry the solid with 10:1 EtOAc/MeOH (10:1. 3 L); filter; collect the solid to provide the title compound as a white solid (300 g). Concentrate the mother liquor to provide additional material. Slurry the this material with a mixture of EtOAc/MeOH (2:1; 1 L) and filter to give an additional 105 g of the title compound as a white solid. Mix the product batches to give the title compound (405 g, 53%). MS (m/z): 182 (M-Cl). ee value 100% (AD-H 250 mm×4.6 mm×5 um column using 90:10 hexanes (with 0.02% DEA):ethyl alcohol at 25° C. with a flow rate of 1.0 mL/min).

Workup

  1. temperaturewhile heating
  2. concentrationconcentrate the mixture
  3. customto give a residue
  4. temperatureheat to 70° C.
  5. stirringwhile stirring for 1 h
  6. concentrationConcentrate the solution under reduced pressure
  7. customto give a residue
  8. filtrationfilter
  9. washand wash the solid with EtOAc (1 L)
  10. customto provide an off white solid
  11. filtrationfilter
  12. customcollect the solid

Sources & evidence

ORD record
ord-7750d5e86463457d941b571d827361e4
Source dataset
uspto-grants-2015_03
Patent number
US08993568B2

Reaction notes

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