Water → 4-(4-Benzyl-morpholin-2-yl)-2-chloro-phenol

HRID 588228Notes

Reaction equation

HRID 588228 reaction equation
[CH2:1]([N:8]1[CH2:13][CH:12]([C:14]2[CH:19]=[CH:18][C:17]([OH:20])=[C:16]([Cl:21])[CH:15]=2)[O:11][CH2:10][C:9]1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].O.[OH-].[Na+]>C1COCC1>[CH2:1]([N:8]1[CH2:9][CH2:10][O:11][CH:12]([C:14]2[CH:19]=[CH:18][C:17]([OH:20])=[C:16]([Cl:21])[CH:15]=2)[CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 666537194-Benzyl-6-(3-chloro-4-hydroxy-phenyl)-morpholin-3-one

Product 1

HCID 666540724-(4-Benzyl-morpholin-2-yl)-2-chloro-phenolYield 76.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-benzyl-6-(3-chloro-4-hydroxy-phenyl)-morpholin-3-one (13.05 g; 39.0 mmol) in THF (600 mL) was added portionwise LiAlH4 (4.44 g; 117.04 mmol) at 0° C. The resulting mixtures was allowed to warm to RT and stirred overnight. Subsequently, the mixture was cooled to 0° C., and water (4.5 mL), a 2M aqueous NaOH-solution (9.0 mL) and water (9.0 mL) were added consecutively. Thereafter the mixture was stirred for 1 h. The formed precipitate was removed by filtration over kieselguhr, and washed with EtOAc. The organic solution was concentrated in vacuo, and the residue purified by column chromatography (SiO2, CH2Cl2/MeOH 98:2) to afford 4-(4-benzyl-morpholin-2-yl)-2-chloro-phenol (9.10 g)

Workup

  1. temperatureSubsequently, the mixture was cooled to 0° C.
  2. stirringThereafter the mixture was stirred for 1 h
  3. customThe formed precipitate was removed by filtration over kieselguhr
  4. washwashed with EtOAc
  5. concentrationThe organic solution was concentrated in vacuo
  6. customthe residue purified by column chromatography (SiO2, CH2Cl2/MeOH 98:2)

Sources & evidence

ORD record
ord-4ce2480c91514aff9b475c1d8c26c73c
Source dataset
uspto-grants-2016_01
Patent number
US09227960B2

Reaction notes

Loading…