tert-Butanol → (6S)-4-benzyl-6-(4-fluorophenyl)morpholin-3-one

HRID 880230Notes

Reaction equation

HRID 880230 reaction equation
[CH2:1]([N:8]([CH2:13][C@H:14]([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1)[OH:15])[C:9](=[O:12])[CH2:10]Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C)(C)C.CC(C)([O-])C.[K+].[Cl-].[NH4+]>O>[CH2:1]([N:8]1[CH2:13][C@H:14]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[O:15][CH2:10][C:9]1=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 25517Ammonium ChlorideHCID 23665647Potassium tert-butoxideHCID 67352707(1S)-1-(4-fluorophenyl)-2-(N-benzyl-N-chloroacetylamino)ethanol

Product 1

HCID 15982164(6S)-4-benzyl-6-(4-fluorophenyl)morpholin-3-oneYield 98%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
22 °C

Procedure

Add N-benzyl-2-chloro-N-[(2S)-2-(4-fluorophenyl)-2-hydroxyethyl]acetamide (1440 g, 4.48 mol) to tert-butyl alcohol (14.5 L) and add potassium tert-butoxide (753 g, 6.73 mol) portion-wise while maintaining the mixture at 22° C. Maintain the mixture at 22° C. and stir for 1.5 hours. Add a saturated aqueous solution of ammonium chloride (1306 g) to quench the reaction. Stir for an additional 1 hour and then add H2O (2 L). Extract with EtOAc (2×10 L); combine the extracts; and concentrate the extracts under reduced pressure provide a residue. Re-dissolve the residue in EtOAc (20 L) and wash with H2O (10 L). Dry the EtOAc solution over Na2SO4 and filter. Collect the filtrate and remove the solvent under reduced pressure to provide the title compound as a colorless oil (1250 g, 98%). MS (m/z): 286 (M+1).

Workup

  1. temperatureMaintain the mixture at 22° C.
  2. customto quench
  3. customthe reaction
  4. stirringStir for an additional 1 hour
  5. extractionExtract with EtOAc (2×10 L)
  6. concentrationand concentrate the extracts under reduced pressure
  7. customprovide a residue
  8. washRe-dissolve the residue in EtOAc (20 L) and wash with H2O (10 L)
  9. dry with materialDry the EtOAc solution over Na2SO4
  10. filtrationfilter
  11. customCollect the filtrate
  12. customremove the solvent under reduced pressure

Sources & evidence

ORD record
ord-ebe9a2bbf1814144a7e66b2ea828d937
Source dataset
uspto-grants-2015_03
Patent number
US08993568B2

Reaction notes

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